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An open, randomized, crossover study in HIV infected patients to evaluate the possible interaction between L- 697,661 and didanosine (ddI).
Baxter JD; Gekowski KM; Kostman JR; Murphy BL; Boruchoff S; Brown I;
December 30, 1995
Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;:135.

Objective: 1) To determine the safety, tolerability, and pharmacokinetics of L-697,661 and ddI given concurrently in multiple doses. 2) To determine if a low fat meal could replace the high fat meal currently recommended with L- 697,661 for drug absorption. Methods: This was an open- label, multiple oral dose, randomized, four-period, crossover study in 15 asymptomatic HIV infected male and female patients with CD4 counts greater than 400 cells/cmm. Patients received each of four treatment regimens with a one a week wash-out between treatment periods: Treatment A- L- 697,661 400 mg q8h for 7 1/3 days, Treatment B- ddI 200 mg q12h for 7 1/3 days, Treatment C- L-697,661 400 mg q8h plus ddI 200 mg q12h for 7 1/3 days, and Treatment D- L-697,661 400 mg single dose with a low fat meal. Acute and steady state pharmacokinetic sampling and safety assessment were done on Day 1 and Day 8 of each treatment period. Patients were questioned for adverse experiences daily during treatments. Results: All patients completed 7 1/3 days of concurrent administration of L-697,661 and ddI. The most commonly reported clinical adverse events with the combination were mild headache, occasional loose stools and mild nausea. There appeared to be no additive toxicity when these two agents were given together. The most commonly reported adverse event with L-697,661 when given alone was mild headache. Other than expected reduction in hemoglobin levels secondary to multiple phlebotomy, there were no laboratory adverse events with these agents given alone or in combination. Conclusion: The combination of L-697,661 and ddI appeared generally well tolerated when taken for a one week period. Data on drug levels will be presented.

Administration, Oral Adult Clarithromycin/ADMINISTRATION & DOSAGE/*PHARMACOLOGY Didanosine/*PHARMACOKINETICS/THERAPEUTIC USE Human HIV Infections/*DRUG THERAPY Radioimmunoassay ABSTRACT