Abstract：
:In vitro data on the metabolism of the antifungal voriconazole suggest that its pharmacokinetics might be influenced by the activity of CYP2C19, CYP2C9, and CYP3A. To elucidate the genetic influence of polymorphic enzymes on voriconazole metabolism, the authors pooled the pharmacokinetic data from 2 interaction studies in which 35 participants were enrolled according to their CYP2C19 genotype to receive a single 400-mg oral dose of voriconazole. Nine participants were homozygous for CYP2C19(*)1/(*)1, 8 heterozygous for (*)1/(*)17, 11 heterozygous for (*)1/(*)2, 2 heterozygous for (*)2/(*)17, 4 homozygous for (*)2/(*)2, and 1 with a double mutation CYP2C19(*)2/(*)2(*)17. Nine (heterozygous) individuals were carriers of the CYP2C9(*)2 or (*)3 variant alleles. Twenty-five participants did not express the CYP3A5 isozyme ((*)3/(*)3), whereas in 5 individuals, the (*)1/(*)3 combination was present (active enzyme). In addition, the CYP2D6 genotype and 2 variants of the drug transporter MDR1 (C3435T and G2677T) were determined. Multiple regression analysis of voriconazole apparent oral clearance revealed that 49% of its variance can be explained solely by the CYP2C19 polymorphism (P < .0001). Including the other polymorphisms into the regression model did not show any significant contribution. The number of variant CYP2C19 alleles therefore explains a substantial part of the wide variability of voriconazole pharmacokinetics, whereas the presence of functional CYP3A5 and the CYP2C9 genotype had no significant impact on voriconazole exposure. Some minor contribution results from the MDR1 C3435T genotype.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Weiss J,Ten Hoevel MM,Burhenne J,Walter-Sack I,Hoffmann MM,Rengelshausen J,Haefeli WE,Mikus Gdoi
10.1177/0091270008327537subject
Has Abstractpub_date
2009-02-01 00:00:00pages
196-204issue
2eissn
0091-2700issn
1552-4604pii
0091270008327537journal_volume
49pub_type
杂志文章abstract：:A vast and continuously growing amount of material on drugs exists in the literature to read and evaluate. Frequently, the papers and their recommendations are conflicting and contradictory. Readers are faced with the dilemma of deciding what to believe. The need for evidence-based medicine as a foundation for optimal...
journal_title：Journal of clinical pharmacology
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doi：
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abstract：:The hydrochlorothiazide component of Maxzide (Lederle Laboratories, Pearl River, NY) has been shown to be more bioavailable than the hydrochlorothiazide component of Dyazide (Smith, Kline and French Laboratories, Philadelphia, PA). The authors compared the antihypertensive effectiveness of a half-tablet of Maxzide (25...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/j.1552-4604.1990.tb03632.x
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abstract：:The centrally acting agents are one of several differing classes of drugs now available for antihypertensive therapy. The availability of newer pharmacologic classes, including the beta-blockers, alpha-blockers. ACE inhibitors and calcium channel blockers, has resulted in a relative decline in the use of the centrally...
journal_title：Journal of clinical pharmacology
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abstract：:Compared with aminoglycosides, chloramphenicol, sulfonamides, tetracyclines, and even penicillins, the cephalosporins represent a remarkably safe class of antibiotics. Among the cephalosporins, the extended spectrum, third generation agents developed generally produce few side effects and appear to be less allergenic ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1990.tb03476.x
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abstract：:Azlocillin is an important acylureido penicillin antibiotic for the management of complex gram-negative infections particularly those caused by Pseudomonas species. The current studies demonstrate that it manifests dose-dependent pharmacokinetics during the usual regimens of clinical dosing, that enterohepatic recircu...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
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doi：10.1002/j.1552-4604.1985.tb02888.x
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1982.tb02645.x
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
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abstract：:Semagacestat, a γ-secretase inhibitor, reduces formation of amyloid beta peptide. Two single-dose (140 mg), open-label, randomized, 3-period, crossover studies evaluated the effect of formulation, food, and time of dosing on the pharmacokinetics and pharmacodynamics of semagacestat in healthy participants. The first s...
journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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doi：10.1002/j.1552-4604.1979.tb01625.x
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abstract：:Amiodarone is an effective antiarrhythmic drug for the control of potentially lethal and lethal ventricular arrhythmias (VA). In the United States, a high-dose regimen has been used at the expense of a high toxicity profile for the control of lethal VAs. Significant antiarrhythmic efficacy has also been established wi...
journal_title：Journal of clinical pharmacology
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abstract：:Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faste...
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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doi：10.1002/j.1552-4604.1981.tb02625.x
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abstract：:Adherence to microbicide gel use is critical to optimizing effectiveness in preventing human immunodeficiency virus transmission. The authors hypothesized that ester taggants added to vaginal gels would generate exhaled alcohol and ketone metabolites and provide a "breath test" for vaginal gel use. This 2-arm (vaginal...
journal_title：Journal of clinical pharmacology
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abstract：:The angiotensin-converting enzyme (ACE) gene is a candidate genetic locus for coronary artery disease (CAD). Studies investigating the relationship between the ACE-insertion/deletion (I/D) gene polymorphism and myocardial infarction (MI) have been inconsistent. The authors hypothesized that age may be an important mod...
journal_title：Journal of clinical pharmacology
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abstract：:To determine the impact of gastric hypoacidity and acidic beverages on delavirdine mesylate pharmacokinetics in HIV-infected subjects, matched subjects with (n = 11) and without (n = 10) gastric hypoacidity received delavirdine 400 mg tid with either water or an acidic beverage (usually orange juice). The pharmacokine...
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abstract：:A treatment gap exists for pediatric patients with renal impairment. Alterations in renal clearance and metabolism of drugs render standard dosage regimens inappropriate and may lead to drug toxicity, but these studies are not routinely conducted during drug development. The objective of this study was to examine the ...
journal_title：Journal of clinical pharmacology
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abstract：:The time course, dose frequency schedule, and dose-response relationship of the citraturic response to orally administered potassium citrate was examined in 22 normal volunteers and 21 patients with uric acid or calcium nephrolithiasis. The slow-release (wax matrix) preparation of potassium citrate produced a rapid an...
journal_title：Journal of clinical pharmacology
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