title: Pharmacokinetics of lamivudine administered alone and with trimethoprim-sulfamethoxazole.
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.
authors.affiliation: School of Pharmacy, University of North Carolina at Chapel Hill 27599-7360, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Moore
authors.forename: G J
authors.initials: GJ
authors.lastname: Yuen
authors.forename: R H
authors.initials: RH
authors.lastname: Raasch
authors.forename: J J
authors.initials: JJ
authors.lastname: Eron
authors.forename: D
authors.initials: D
authors.lastname: Martin
authors.forename: P K
authors.initials: PK
authors.lastname: Mydlow
authors.forename: E K
authors.initials: EK
authors.lastname: Hussey
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006679:HIV Seropositivity / Q000378:metabolism*; D006801:Humans; D019259:Lamivudine; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000652:urine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D016047:Zalcitabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D016047:Zalcitabine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination