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Clin Pharmacol Ther. 1996 May;59(5):550-8.

Pharmacokinetics of lamivudine administered alone and with trimethoprim-sulfamethoxazole.

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1
School of Pharmacy, University of North Carolina at Chapel Hill 27599-7360, USA.

Abstract

OBJECTIVE:

To determine the effect of multiple dosing of combined sulfamethoxazole and trimethoprim on the single-dose pharmacokinetics of lamivudine.

METHODS:

Fourteen subjects with human immunodeficiency virus who had CD4+ cells > or = 200/mm3 received two single doses of 300 mg lamivudine, separated by 7 to 14 days, in a randomized two-day crossover study. Treatment consisted of lamivudine alone versus trimethoprim-sulfamethoxazole (160/180 mg) daily on days 1 through 4 followed by lamivudine plus trimethoprim-sulfamethoxazole on day 5. Blood and urine were collected over 24 to 32 hours to determine lamivudine, trimethoprim, sulfamethoxazole, and N-4-acetylsulfamethoxazole concentrations.

RESULTS:

Coadministration of a single dose of lamivudine and trimethoprim-sulfamethoxazole after daily dosing for 5 days altered the pharmacokinetics of lamivudine. A 43% increase in area under the concentration-time curve (AUC infinity) and a 35% decrease in renal clearance (CLR) were observed when lamivudine was coadministered with trimethoprim-sulfamethoxazole compared with lamivudine alone. The geometric least-squares trimethoprim-sulfamethoxazole were as follows: AUC infinity, 10,124 (9,432-10,866) and 14,448 (13,461-15,508) ng . hr/ml, respectively; CLR, 16.6 (14.1-19.4) and 10.8 (9.5-12.6) L/hr, respectively. Coadministration did not significantly alter the pharmacokinetics of trimethoprim or sulfamethoxazole.

CONCLUSIONS:

Coadministration of lamivudine with trimethoprim-sulfamethoxazole resulted in an increased AUC infinity and a decreased CLR of lamivudine. However, given the favorable safety profile of lamivudine, it is unlikely that this interaction will result in a significant increase in concentration-related toxicity at the doses studied.

PMID:
8646826
DOI:
10.1016/S0009-9236(96)90183-6
[Indexed for MEDLINE]

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