Effect of indinavir on the single-dose pharmacokinetics of theophylline in healthy subjects.
The effect of multiple doses of indinavir on the pharmacokinetics of a single dose of theophylline was investigated in 16 healthy male subjects using a randomized, double-blind, placebo-controlled, parallel-group study design. On days 1 and 7, all of the subjects received a single oral 250 mg dose of theophylline. From days 2 to 7, the subjects received orally administered 800 mg doses of indinavir or a matched placebo every 8 hours. On day 7, theophylline and indinavir (or a placebo) were coadministered. The geometric mean AUC(0-24 h) of theophylline increased 18% when coadministered with indinavir compared to when theophylline was administered alone. This small increase in AUC(0-24 h), although considered statistically significant, did not meet the prespecified criterion for clinical significance. The geometric mean Cmax of theophylline, when coadministered with indinavir, was within 8% of theophylline when administered alone. The mean tmax (+/- SD) value for theophylline, when coadministered with indinavir (0.9 +/- 0.5 h), was comparable to that observed for theophylline alone (1.0 +/- 0.5 h). In conclusion, the administration of multiple doses of indinavir followed by a single dose of theophylline did not appear to result in a clinically significant pharmacokinetic interaction for theophylline.
Mistry
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Merck Research Laboratories, Department of Clinical Pharmacology, Rahway, New Jersey 07065, USA.
Laurent
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A
Sterrett
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Deutsch
P J
PJ
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology*; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004347:Drug Interactions; D006801:Humans; D019469:Indinavir / Q000009:adverse effects / Q000494:pharmacology*; D008047:Lip Diseases / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D013806:Theophylline / Q000009:adverse effects / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D001993:Bronchodilator Agents; D019469:Indinavir; D013806:Theophylline