Trimethoprim, alone or in combination with sulphamethoxazole, decreases the renal excretion of zidovudine and its glucuronide.
Trimethoprim and trimethoprim-sulphamethoxazole (co-trimoxazole) are often prescribed in HIV patients treated with zidovudine. The pharmacokinetics of zidovudine, after a dose of 3 mg kg-1 by constant rate intravenous infusion over 1 h were evaluated in nine HIV patients in an open, randomized, three-phase crossover study, without and with trimethoprim (150 mg) and trimethoprim-sulphamethoxazole (160 and 800 mg). The metabolic clearance of zidovudine was not significantly influenced by trimethoprim-sulphamethoxazole and trimethoprim. However, the renal clearance of zidovudine was decreased by 58 and 48%, respectively, and that of its glucuronide by 27 and 20% (P < 0.05). The fraction of the dose excreted as the parent compound fell by 47 and 39% and the metabolic ratio by 48 and 43% (P < 0.05). This kinetic drug interaction, apparently due solely to trimethoprim, may only be clinically important when hepatic glucuronidation is also impaired by liver disease or inhibited by other drugs.
Chatton
J Y
JY
Département de Médecine interne, Centre Hospitalier Universitaire Vaudois, Switzerland.
Munafo
A
A
Chave
J P
JP
Steinhäuslin
F
F
Roch-Ramel
F
F
Glauser
M P
MP
Biollaz
J
J
D000328:Adult; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D014295:Trimethoprim / Q000008:administration & dosage / Q000494:pharmacology*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000494:pharmacology*; D015215:Zidovudine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000652:urine*
D015215:Zidovudine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014295:Trimethoprim; C055886:3'-azido-3'-deoxy-5'-O-beta-glucopyranuronosylthymidine