1. Nifedipine was administered to eight volunteers (seven Caucasian, one East Asian of Chinese origin) as a single 10 mg capsule orally and as 2.5 mg intravenously. The pharmacokinetics were determined under fasting conditions and following 200 ml double strength grapefruit juice taken orally both 2 h before and at the time of dosing. 2. In a separate study, the pharmacokinetics of nifedipine were defined in eight South Asian volunteers (with both parents originating from the Indian subcontinent) following 10 mg nifedipine orally and 2.5 mg intravenously. 3. The administration of grapefruit juice did not alter the pharmacokinetics of intravenous nifedipine, but resulted in a significantly increased area under the plasma concentration‐time curve (AUC) (191 +/‐ 59 c.f. 301 +/‐ 95 ng ml‐1 h, P < 0.05) and bioavailability (0.63 +/‐ 0.18 c.f. 0.86 +/‐ 0.15, P < 0.05) following oral nifedipine. The elimination half‐life was unchanged by administration of grapefruit juice and there was no evidence of decreased formation of the nitropyridine first‐pass metabolite. 4. The AUC of nifedipine after intravenous administration was significantly higher in South Asian subjects than in Caucasians (146 +/‐ 39 c.f. 74 +/‐ 18 ng ml‐1 h, P < 0.002). This was due to a lower systemic clearance in the South Asians which was 50% of that in the Caucasians. The half‐life was markedly prolonged in South Asians (4.1 +/‐ 1.9 c.f. 1.7 +/‐ 0.5 h, P < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of probenecid on the combination of amoxycillin/clavulanic acid has been compared with the effect on amoxycillin alone and it has been shown that probenecid, whilst producing its expected effect on amoxycillin, did not affect the clavulanic acid concentration of the combination. A possible minor role for tubular secretion of clavulanic acid is discussed.

Abstract:One of the great advances in the treatment of HIV-1 infection was the development of the highly active antiretroviral therapy (HAART). Although this treatment strategy is highly effective in many individuals, interpatient variability of drug response and high incidences of short-and long-term toxicities remain significant problems associated with this treatment. Logically, pharmacogenetic differences among HIV-1-infected individuals are thought to represent important factors contributing to antiretroviral drug response. Studies have identified polymorphisms in drug-metabolizing enzymes, drug transporters, and most recently the human leukocyte antigen locus that appears to have significant effects on the clinical outcomes of antiretroviral therapy. Furthermore, some studies have shown that many of these crucial polymorphisms are more likely or less likely in certain populations. This review investigates the potential role of pharmacogenomics in the management of HIV-1 infection in people of African descent.

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