Proscar

Fairmont State College. E. Kadok, MD: "Purchase online Proscar cheap no RX - Effective online Proscar OTC".

Premature labour: Gluc 5% should be used to prepare the infusion to #risk of maternal pulmonary oedema generic proscar 5 mg on line prostate gleason score. More than 10 micrograms/minute is rarely required; 20 micrograms/minute should not be exceeded buy proscar 5 mg overnight delivery man health in hindi. Dose in renal impairment: adjusted according to creatinine clearance:1 * CrCl >20--50mL/minute: reduce the parenteral dose by 50% cheap 5 mg proscar free shipping man health issues. Terbutaline sulfate | 805 Continuous intravenous infusion via a syringe pump Preparation of a 100 micrograms/mL solution (other strengths may be used according to local policies) 1 order proscar 5mg with visa prostate cancer quiz and answers. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Continuous intravenous infusion (large volume infusion) Preparation of a 5 micrograms/mL solution (other strengths may be used according to local policies) 1. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Technical information Incompatible with No information Compatible with Flush: NaCl 0. Stability after From a microbiological point of view, should be used immediately; however, prepared preparation infusions may be stored at 2--8 C and infused (at room temperature) within 24 hours. Additional information Common and serious Immediate: Hypersensitivity reactions have been reported. Action in case of The preferred antidote is a cardioselective beta-blocker, but use with caution in overdose patients with a history of bronchospasm. This assessment is based on the full range of preparation and administration options described in the monograph. Teriparatide | 807 Teriparatide 250 micrograms/mL solution in 3-mL pre-filled multidose pen (28 doses) * Teriparatide is a recombinant fragment of human parathyroid hormone. Pre-treatment checks * Avoid in pre-existing "Ca, severe renal impairment, metabolic bone diseases including hyperpara- thyroidism and Paget disease, skeletal malignancies or bone metastases or previous radiation therapy to the skeleton. Dose in renal impairment: no dose adjustment required in mild impairment; use with caution in moderate impairment; do not give in severe renal impairment. Technical information Incompatible with Not relevant Compatible with Not relevant pH Not relevant Sodium content Negligible Excipients Contains metacresol (may cause hypersensitivity reactions). In use: Once opened, the pen should be used for a maximum of 28 days and then discarded. Urinary calcium Periodically * In patients with suspected active urolithiasis or pre-existing hypercalciuria. Additional information Common and serious Immediate: Hypersensitivity reactions: acute dyspnoea, facial oedema, undesirable effects generalised urticaria, chest pain, oedema (mainly peripheral). Antidote: No known antidote; stop administration and give supportive therapy as appropriate. This assessment is based on the full range of preparation and administration options described in the monograph. Terlipressin | 809 Terlipressin 1-mg dry powder vial with 5mL solvent 120 micrograms/mL (1mg/8. Pre-treatment checks Caution in patients with hypertension, atherosclerosis, cardiac dysrhythmias or coronary insufficiency. Hepatorenal syndrome (unlicensed): 1mg every 4--12 hours for 7--15 days appeared to improve renal function. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Technical information Incompatible with No information Compatible with Flush: NaCl 0. Displacement value Negligible Stability after Use reconstituted vials immediately. Fluid balance * Terlipressin has approximately 3% of the antidiuretic effect of vasopressin and could cause fluid retention and #Na. This assessment is based on the full range of preparation and administration options described in the monograph. Testosterone and esters | 811 Testosterone and esters Sustanon 250 (mixed testosterone esters 250mg) oily solution in 1-mL ampoules Testosterone enantate 250mg/mL oily solution in 1-mL ampoules Testosterone propionate 50mg/mL oily solution in 2-mL ampoules Testosterone undecanoate 250mg/mL oily solution in 4-mL ampoules * Testosterone is a hormone with anabolic and androgenic properties. Pre-treatment checks * Avoid in breast cancer in men, prostate cancer, past or present liver tumour, and "Ca. A second injection may be given after 6 weeks depending upon testosterone levels and clinical symptoms. Intramuscular injection Contains arachis oil -- should not be given in peanut allergy. Monitoring Measure Frequency Rationale Signs and symptoms Once or twice a year * Review for prostate/breast cancer. Serum Na and Ca * May cause electrolyte disturbances including Na retention with oedema and "Ca. Signs of osteoporosis * Especially in patients who have undergone oophorectomy (e. Testosterone and esters | 813 Additional information Common and serious Immediate: Testosterone enantate and undecanoate -- rarely coughing, undesirable effects dyspnoea and circulatory irregularities may occur. With testosterone enantate these symptoms may be reduced by injecting very slowly. Other: Polycythaemia, weight gain, hot flush, acne, prostate abnormalities and prostate cancer. Sustanon is a combination of different esters of testosterone with different durations of action. Action in case of Stop treatment; once symptoms have disappeared consider resuming at a lower overdose dose. Counselling Female patients should be asked to report any signs of virilisation such as acne, hirsutism and voice changes. Male patients: if frequent or persistent erections occur, the dose should be reduced or the treatment discontinued to avoid injury to the penis. This assessment is based on the full range of preparation and administration options described in the monograph. Biochemical and other tests In diagnostic testing, measure plasma cortisol concentration immediately before giving the dose. Measure plasma cortisol concentration immediately before the dose, and exactly 30 minutes afterwards. Adrenocortical function is considered normal if the plasma cortisol concentra- tion rises by 200 nanomol/L (70 micrograms/L) or more. Measure plasma cortisol con- centrations immediately before the dose, and exactly 30 minutes and 1, 2, 3, 4 and 5 hours afterwards. Interpretation: the 5-hour test is used where the 30-minute test is inconclusive or where it is necessary to determine the functional reserve of the adrenal cortex. Adrenocortical function is considered normal if the plasma cortisol concentration increases 2-fold in the first hour, and continues to rise steadily. The values expected would be 600--1250 nanomol/L in thefirsthour, increasing slowly upto1000--1800 nanomol/Lbythefifth hour.

The paradox generic proscar 5 mg online prostate cancer and sexual dysfunction, however cheap 5mg proscar amex prostate what does it do, lies in the fact that contrary to expectation purchase 5 mg proscar with amex prostate 5 2, normal tissues are often regenerated faster than cancer cells discount proscar 5 mg amex prostate cancer 9 on gleason scale. Therefore, after the cytoinhibitory action of certain drugs, normal tissues can be restored after chemotherapy. Drugs used to treat cancer are subdivided into six groups: antimetabolites, alkylating agents, antibiotics, drugs isolated from plants, hormones, and a group of substances not included in the classifications listed above, which are examined in another section. So, by competing with natural pyrines and pyrimidines in metabolic schemes, they interfere with the synthesis of nucleic acids, thus being included in place of ordinary metabolites. This leads to the formation of cellular products, which cannot function nor- mally. In addition, because they are structural analogs of natural substances, antimetabolites can act not only by being introduced into the metabolic process and form “false” non- functional metabolites, but also by inhibiting catalytic functions of certain enzymes or enzyme systems. Antimetabolites are subdivided into three groups: folic acid antagonists (methotrexate), purine antagonists (mercaptopurine, thioguanidine), and pyrimidine antagonists (fluo- rouracil, floxuridine, cytarabine). This is the general starting compound for enzyme-catalyzed reactions of transferring a methyl group. Folates are carriers of a sin- gle carbon group (methylating group) necessary during purine and pyrimidinethimidylate synthesis, and in particular for methylating deoxyuridine monophosphate to deoxythimidine monophosphate. Dihydrofolate reductase’s affinity with antimetabolics is much higher than with usual substrates—folic acid and its reduced forms. Because of the pronounced affinity of dehydrofolatereductase to methotrexate, even large doses of folic acid introduced simul- taneously turn out to be useless in preventing the effects of methotrexate. This undergoes reductive methylation using formaldehyde and hydrogen, which forms N-(4-methylaminobenzoyl)glutamic acid (30. The second part of the methotrexate molecule, 2-amino-4-hydroxy-6-bromomethylpteri- dine (30. This is nitrosylated by anhydrous nitrous acid to 2,4,6-triamino-5-nitrosopyrimidine (30. Upon reacting this with 1,2- dibromopropionic aldehyde, the product of attaching bromine to acrolein, 2-amino-4- hydroxy-6- bromomethyl-pteridine (30. Synonyms of this drug are farmitrexate, ledertrexate, ematexate, maxtrex, folex, mexate, and others. These compounds inhibit synthesis of purine nucleotides, which are made up of purine bases and phosphorylated ribose. Both compounds must be transformed into nucleotides by adding a phosphoribosyl fragment. Upon reacting phosphorous pentachlo- ride with uric acid, 2,6,8-trichloropurine (30. The three chlorine atoms in trichloropurine differ significantly in terms of reactivity for nucleophilic substitution. The chlorine atom at C6 is much more active than the chlorine atom at C2, and this is more active than the chlorine atom at C8, which allows subsequent manipulation by them. Upon reaction with phosphorous pentasulfide, hypoxanthine is transformed into mercaptopurine (30. Mercaptopurine is used for treatment of lymphobastomas, myeloblastoma leucosis, and to treat neuroleukemia. Replacement of the hydroxyl group with a mercapto group at C6 is carried out by reacting it with phosphorous pentasulfide, which forms thioguanine (30. Mercaptopurine is important as a drug of supportive therapy in treatment of both adults and children. Thioguanine may have specific clinical use, or may be used in combination with other drugs in severe myelogenous therapy. This action is accom- panied by formation of an active metabolite, 5-fluorodeoxyuridinomonophosphate from both fluorouracil and fluoxuridine. This complex inhibits thymidylate sythetase and reduces methylation of 2-deoxyuridine acid for formation of thymidylic acid. Antineoplastics 5-fluorouracid is direct fluorination of uracil with fluorine or trifluoromethylhypofluoride [23–28]. Fluorouracil is used to treat carcinomas of the head, neck, colon, rectum, breast, stom- ach, bladder, pancreas, and for actinic and solar creatitis. Synonyms of this drug are efflu- derm, fludix, fluoroblastin, arumel, benton, lifril, and others. Like other pyrimidine antimetabolites, cytarabine must be “activated” by initially transforming into the corre- sponding nucleotide. In principle, however, alkylation can occur and occurs at O6 or N3 of guanine, at N1,N3, or N7 of adenine, or at N3 of cytosine. The schematic mechanism of the action of alkylating drugs, mechlorethamine for exam- ple, the most simple of them all, can be explained by the following scheme. They can be classified as nitrogen-containing mustard derivatives (mechorethamine, chlorambucil, melfalan, cyclophosphamide, ifos- famide), derivatives of ethylenimine (thiotepa), nitrosoureas (carmustine, lomustine, strep- tozocin), alkylsulfonates (busulfan), and derivatives of platinum (cisplatin, carboplatin). Synonyms of this drug are azotoyperit, chlorethamine, chlorethazide, mustine, and many others. In the first stage of synthesis, acetanilide is acylated by succinic anhydride, giving 4-(4-acetaminophenyl)-4-ketobutyric acid (30. The keto group in this compound is reduced by hydrogen in a methanol solution using palla- dium on carbon as a catalyst. This results in the formation of the methyl ester of 4-(4-aceta- minophenyl)-butyric acid (30. This is treated with an alkali in order to hydrolyze both the amide and ester parts of the molecule, which forms 4-(4-aminophenyl)butyric acid (30. Replacing all of the hydroxyl groups in this compound using phosphoryl chloride and subsequent treatment with water to hydrolyze the resulting intermediate acid chloride to an acid gives chlorambucil (30. Reacting this with an ethanol in the presence of hydrogen chloride gives the hydrochloride of 4-nitro-L-phenylalanine ethyl ester (30. The nitro group in this molecule is reduced to an amino group using palladium on calcium carbonate as a catalyst. The hydroxy groups in this molecule are replaced with chlorine atoms upon reaction with thionyl chloride, after which treatment with hydrochloric acid removes the phthalamide protection, giving melphalan (30. The racemic form of this drug, D,L-3-[p-[bis-(2-chloroethyl)amino]phenyl]alanine, is also widely used under the name sarcolysine or racemelfalan. Present in the blood, it is practically inactive, although upon penetrating cancerous cells 398 30. Antineoplastics and reacting with a relatively large number of phosphamidases, it cleaves, essentially releasing a cytostatic substance, bis-(2-chloroethyl)amine. This means that the alkylating action of this drug is specifically directed toward can- cerous cells. It is used for chronic lym- phatic leukemia, Hodgkin’s disease, Burkitt’s lymphoma, multiple myeloma, and cancer of the breast, neck, ovaries, and so on. Synonyms of this drug are endoxan, cyclostin, cytoxan, cyclophosphane, and others.

Proscar 5 mg with mastercard. The Try Guys Get Prostate Exams.

proven proscar 5mg

Panicum caffrorum (Broom Corn). Proscar.

What is Broom Corn?
Dosing considerations for Broom Corn.
How does Broom Corn work?
Digestive disorders and other uses.
Are there safety concerns?

Source: http://www.rxlist.com/script/main/art.asp?articlekey=96592

In those latter times hallucinogens were popularly identiﬁed with beatniks and hippies cheap 5 mg proscar otc androgen hormone in female, and social disapproval of those lifestyles promoted legal restrictions on hallucinogens that terminated almost all sci- entiﬁc research regarding these substances generic proscar 5mg otc mens health aus. First order 5 mg proscar with mastercard man health network, despite easy availability effective proscar 5mg mens health towie, inhalants are among the most dangerous of abused substances. There is no range of inhalants, some of which are benign and some of which are risky, as there is with stimulants or depressants. All inhalants are dangerous despite wide var- iations in their chemistry, and this sets them apart from other types of drugs. Second, inhalants are generally used by inhaling them in their gaseous state (which is not the same as smoking and also differs from eating a solid or drinking a liquid). Third, inhalants are used mainly by younger persons (typically teenage males), a usage pattern that also sets inhalants apart from other drugs. With some inhalants the amount needed to produce a recreational effect is close to a fatal dose, and deadly outcomes demonstrate that the difference was too close for some deceased users to handle. In addition, strenuous exercise seems related to inhalant death, troublesome for users at dance clubs. The products are often ﬂammable, sometimes producing serious physical injury unrelated to pharmacology. Some users act as if they do not realize they need a continual supply of oxygen, and they administer inhalants in ways that cause suffocation. In addition to all these acute dangers, long-term use of many inhalants can produce nerve damage, impairing the ability to use arms and legs and hands and feet, damage veriﬁed scientiﬁcally. This conse- quence is harder to verify because inhalant users often take other potent drugs, so proving which mind-altering drug affected the mind can be very difﬁcult. Unquestionably, however, inhalant users can develop states of mind interfer- Drug Types 27 ing with—or even preventing—their ability to function in society. Admittedly, some users avoid serious outcomes, just as some car drivers run red lights without harm. Generally, adult drug users shun most inhalants except as a choice of des- peration if nothing else is available. Inhalant users tend to be teenagers or younger, perhaps because other drugs of abuse (even alcohol and tobacco) are harder for some young persons to obtain. Snifﬁng is often a social event with acquaintances rather than a solitary pastime. Another study found glue sniffers to have personalities matching those of alcoholics. Case studies of butane sniffers tell of lonely persons with difﬁculties at school or at home. A psychological test of 59 inhalant abusers47 found them to be impulsive persons with little respect for authority. Most research ﬁnds inhalant users to be unhappy persons mar- ginalized by society. Yet not all researchers ﬁnd that inhalant users are social misﬁts from dysfunctional families; some appear to be ordinary persons, though still youthful. That difference in ﬁndings—most researchers saying inhalant abusers are social misﬁts, with some researchers contending inhalant abusers are normal— deserves an attempt at explanation. Many inhalant researchers work where inhalant abuse has been publicized as a major community problem, and those places tend to have populations of socially marginalized people. Researchers commonly study persons receiving medical attention for inhalant abuse, and sometimes the medical attention is received involuntarily by court order. Such persons may be no more typical of inhalant users than hospitalized alcoholics receiving court-ordered treatment are typical of most alcohol users. A user who sniffs several times a day is not the same kind of user who sniffed with some friends once or twice over a period of several years. Although most research ﬁnds inhalant abusers to be troubled outcasts, it is possible that such typical ﬁndings are due to the demographics of the population being studied. Czerwinski, “Amphetamine-Related Disorders,” Journal of the Louisiana State Medical Society 150 (1998): 491; R. Reeves, President Kennedy: Proﬁle of Power (New York: Simon & Schuster, 1993), 178, 243, 648n. Reeves, A Question 28 The Encyclopedia of Addictive Drugs of Character: A Life of John F. Jackson, “The Amphetamine Inhaler: A Case Study of Medical Abuse,” Journal of the History of Medicine and Allied Sciences 26 (1971): 187–96. The author is also indebted to Jackson’s article for other colorful examples of amphetamine’s history. Plessinger, “Prenatal Exposure to Amphetamines: Risks and Adverse Outcomes in Pregnancy,” Obstetrics and Gynecology Clinics of North America 25 (1998): 119–38. Apovian, “The Use of Pharmacologic Agents in the Treatment of the Obese Patient,” Journal of the American Osteopathic Association, pt. Hinkle, “The Effect of Expectation on Response to Phen- metrazine,” Psychosomatic Medicine 26 (1964): 369–73. Hollister, “Phenmetrazine: An Obsolete Problem Drug,” Clin- ical Pharmacology and Therapeutics 32 (1982): 672. Population–Based Sample of Male Twins,” Archives of General Psychiatry 57 (2000): 261–69. Coutinho, “Transtornos mentais como fatores de risco para o desenvolvimento de abuso/dependeˆncia de cocaı´na: Estudo caso-controle” (Mental disorders as risk factors for the development of cocaine abuse/dependence: Case- control study), Revista de Saude Publica 33 (1999): 477–86 (abstract in English). Wisner, “Methamphetamine Use in Trauma Patients: A Population-Based Study,” Journal of the American College of Surgeons 189 (1999): 442–49. Chen, “Extent of Smoking and Nicotine Dependence in the United States: 1991–1993,” Nicotine and Tobacco Research 2 (2000): 263–74. Cheng, “Substance Use Disorders among Ad- olescents in Taiwan: Prevalence, Sociodemographic Correlates and Psychiatric Comor- bidity,” Psychological Medicine 29 (1999): 1387–96. College Students’ Use of Tobacco Products: Results of a National Survey,” Journal of the American Medical Association 284 (2000): 699–705. Mahowald, “Long-Term, Nightly Benzodiazepine Treat- ment of Injurious Parasomnias and Other Disorders of Disrupted Nocturnal Sleep in 170 Adults,” American Journal of Medicine 100 (1996): 333–37. Ciraulo, “Abuse Potential of Benzodiazepines,” Bulletin of the New York Academy of Medicine 61 (1985): 728–41. Nel, “Die Afhanklikheidspotensiaal van die Bensodiasepiene: Toepassing van die Resultate van die Behandeling van die Alkoholonttrekkingsind- room” (The addiction potential of benzodiazepines. Application of the results of treat- ment of alcohol withdrawal syndrome), South African Medical Journal 59 (1981): 115–16 (abstract in English). Nel, “Pharmacological Requirements of Patients during Alcohol Withdrawal,” South African Medical Journal 59 (1981): 114. Hansen, “Benzodiazepines Enhance the Consumption and Palatability of Alcohol in the Rat,” Psychopharmacology 137 (1998): 215–22. Lundberg, “The Effect of Benzodiazepines on the Fetus and the Newborn,” Neuropediatrics 23 (1992): 18–23.

purchase proscar 5 mg fast delivery

Alternatively proscar 5 mg generic androgen hormone x organic, a caffeine breath test can similarly provide such within-subject information buy proscar 5 mg prostate oncology fellowship. Activity is localized mainly in the liver; however 5 mg proscar prostate 60, extrahepatic distribution is also present quality proscar 5mg prostate symptoms, especially in the nasal epi- thelium and lung. The 7-hydroxylation of coumarin (1,2-benzopyrone) is a major urinary metabolic pathway that accounts for about 60% of an orally administered dose (102). The phenotypic trait measure is simply the percentage of a 5-mg dose of coumarin excreted in urine as 7-hydroxycoumarin over the zero- to two-hours period following oral administration in the fasted state (102). Because the 7-hydroxy metabolite is excreted mainly as a conjugate, urine is pretreated with b-glucuronidase prior to analysis, and a methodology based on chromatographic separation would appear to be preferable to one using solvent extraction (103). Application of this phenotyping procedure to various population groups has shown that the trait measure exhibits considerable interindividual variability, and it is unimodally distributed in a normal fashion (102–104). Accordingly, it would be expected that in the general population all three phenotypes (extensive, intermediate, and poor) would be present. First, is the fact that the trait value is entirely empirical and has been validated and characterized to only a very limited extent. As expected, severe but not mild liver disease reduces the urinary recovery of 7-hydroxycoumarin, but, not unexpect- edly, renal dysfunction has also been found to affect the trait value (109). This is because of the extreme analytical difficulties associated with measuring plasma coumarin levels because of its relatively high volatility, and this problem is further compounded by the low dose used for phenotyping (5 mg). Coumarin is also excreted in the urine as a result of dietary and environmental exposure through fragrances and other sources. Such daily exposure may be as high as 25 mg (110), which probably accounts for the finding that in certain subjects the urinary molar recovery of 7-hydroxycoumarin exceeds the molar dose of cou- marin administered to determine the trait value (103,110). An additional con- sideration, especially in North America, is the absence of an available approved formulation containing coumarin, which was removed from the market 45 years ago because of its hepatotoxicity and carcinogenic properties in animals (111). More recently, limited use of coumarin in certain types of cancer has been investigated (112), but the strength of the available tablet is 100 mg, i. The frequency distribution of this trait measured in 103 subjects identified two individuals with values markedly greater than the remainder of the population. Moreover, within the major subgroup, there was evidence of overlapping bimodality. The major human urinary metabolites of nicotine are cotinine, nicotine N -0 oxide, and trans-3 -hydroxycotinine0 (113). One reported approach is based on the 30-minute intravenous infusion of a 50:50 mixture (2 mgbase/kg)of3,3 -dideuterium-labeled0 0 nicotine and 2,4,5,6-tetradeutero cotinine followed by serial blood sampling over the following 96 hours and a 0- to 8-hour urine collection (116,117). Using gas chromatography–mass spectrometric–based assays, the levels of nicotine and cotinine derived from each stable-labeled form are measured. Appropriate pharmacokinetic anal- ysis then allows estimation of nicotine’s formation clearance to cotinine and also the latter’s clearance. To date, this methodology has been applied primarily to investigating nicotine’s metabolism within the context of cigarette smoking and addiction (116,117). Despite the need for stable-labeled drugs and the associated sophisticated instrumentation for their measurement, such an approach would provide a gold-standard against which alternative trait measures such as the coumarin index or others could be evaluated and validated. Possibly, a simpler, single-point plasma- or urine-based measure could be developed using nicotine/cotinine. Accordingly, these two isoforms have received the most attention with regard to the development and application of in vivo probes. Such drugs for which the isoform catalyzes the formation of a principal metabolite include phenytoin, tolbutamide, fluoxetine, losartan, S-warfarin, torsemide, valproic acid, and many nonsteroidal anti-inflammatory agents (diclofenac, ibuprofen, naproxen, piroxicam, suprofen, and tenoxicam). Furthermore, this difference has also been noted to be present in patients receiving warfarin therapy, where a gene-dose effect leads to reduced clearance of the anticoagulant’s S-enantiomer (120–122). However, for safety and analytical reasons, it is unlikely that the anticoagulant could be used as an in vivo probe in healthy subjects. Tolbutamide The metabolism of tolbutamide (l-butyl-3-p-tolysulfonylurea) in humans in- volves a single pathway, with the initial and rate-limiting step being tolyl methyl-hydroxylation to form hydroxytolbutamide, which is further oxidized to carboxy-tolbutamide by alcohol and aldehyde dehydrogenases. Since the drug’s half-life ranges between 4 and 12 hours, this approach requires not only multiple blood samples but collection over a considerable time period (24–36 hr). However, such use is not without problems, in par- ticular, the safety issue associated with the hypoglycemic response produced by tolbutamide administration. However, in fasted individuals, blood glucose levels may be sig- nificantly reduced by tolbutamide and require reversal using glucose supple- mentation (130); use of a lower dose (250 mg) may obviate this problem. Unfortunately, validation of neither of these putative trait measures using diclofenac has been reported. Such preliminary information will obviously require appropriate substantiation before the descri- bed trait measures will be widely accepted. Although, its substrate specificity was originally thought to be limited to related anticonvulsant agents, the in vivo metabolism of an increasing number of structurally unrelated drugs appear to be mediated by this isoform. These include R-mephobarbital (4 -hydroxylation)0 (135), hexobarbital (3 -hydroxylation) (136),proguanil (ring cyclization)(137),omeprazole, and related0 proton pump inhibitors (5 -methylhydroxylation)0 (138–140), diazepam (N-demethylation) (141), certain tricyclic antidepressants (N-demethylation) (142–144), carisoprodil (N-dealkylation) (145), citalopram (N-demethylation) (146), moclobemide (C-hydroxylation) (147), propranolol (side-chain oxidation) (148), and nelfinavir (methylhydroxylation) (149). A similar low prevalence rate is also present in Africans and African Americans (161–163). By contrast, a much higher frequency (13–23%) is found in indigenous populations living in Southeast Asia, such as Chinese, Japanese, and Koreans (138,164–168). These factors have led to the development of in vivo probes to classify individuals according to phenotype. Subsequently, two alternative phenotyping procedures were developed that have been widely used throughout the world by numerous investigators. The 4 -hydroxylation0 of S-mephenytoin is not only extensive but also rapid, and this is in contrast to metabolism of the R-enantiomer, which involves mainly N-demethylation (150). The pharmacokinetic basis of the trait measure has been described, and studies have confirmed that the urinary S:R ratio is the same as the comparable ratio of the areas under the plasma concentration–time profiles of the enantiomers during the collection period, which in turn reflects the relative 604 Wilkinson intrinsic clearances of the two isomers (169). Also, this trait value has been found to be reproducible in individuals over a long period of time (170). For this reason, there is some merit in using the R:S ratio, which is linearly related to such activity, so the smaller its value, the lower the 4 -hydroxylating0 activity (21,171). A minor route of metabolism of S-mephenytoin results in the formation and urinary excretion of an acid-labile conjugate that is probably a cysteinyl derivative (172). The significance of this urinary metabolite is that it is easily hydrolyzed back to S-mephenytoin, and this can occur to an unpre- dictable extent during sample storage, even at À208C (173). The resulting artifactual S:R ratio value may, therefore, misclassify an individual’s phenotype. The most widely used procedure is to obtain a repeat S:R value but following acid hydrolysis of the urine sample prior to analysis. Another approach (176) includes measurement of the S:R ratio in a urine sample collected 24 to 32 hours after drug administration, since little or no acid-labile metabolite is present at this time. Also, it is possible to extract the collected urine immediately after collection and store the dried extract at À208C until subsequent analysis (176). For this reason, an alternative phe- notypic trait measure based on the formation and urinary elimination of 4 -0 hydroxymephenytoin has also been frequently used.