Lambert J, Dolin R, Seidlin M, Knupp C, McLaren C, Reichman RC; International Conference on AIDS.
Int Conf AIDS. 1989 Jun 4-9; 5: 563 (abstract no. M.C.P.130).
University of Rochester, Rochester, NY, USA
OBJECTIVE: To determine the maximum tolerated dose (MTD) and pharmacokinetics of ddI in patients with AIDS or AIDS related complex (ARC). METHODS: In a phase I trial, ddI is being administered IV for 2 weeks and po for 8-15 weeks to patients with AIDS or ARC at escalating dose levels. Initial doses were 0.4 mg/kg IV q12h followed by 0.8 mg/kg po q12h, and have currently been escalated to 3.0 mg/kg IV and 6 mg/kg po, with additional escalations being planned until the MTD is reached. Clinical, pharmacokinetic, and laboratory parameters are being followed, including serial HIV cultures, serum p24 antigen and lymphocyte markers. RESULTS: 12 patients have been studied for 2-15 weeks, including 3 at the 3 mg/kg IV dose. ddI has been well tolerated at all dose levels without adverse clinical effects. There have been no significant effects on Hb, WBC, liver function tests, BUN on platelets, except for 1 subject at the initial dose level who developed thrombocytopenia, possibly related to ddI. Of patients followed for at least 10 weeks, 2/6 had an increase in CD4 cells/ml, from 106 to 160 and from 237 to 513, and one had a serum p24 antigen decrease from 215 pg/ml to 134. At 1.0 mg/kg IV and 2.0 mg/kg po, the Cmax was 980 and 812 ng/ml. The Tmax was 0.82 hrs after oral dosing. CONCLUSION: Up to doses currently administered, ddI appears to be well tolerated in terms of both clinical and laboratory parameters. Comparable plasma concentrations are achieved when twice the IV dose is given orally. Additional dose escalations to reach the MTD are underway.
Publication Types:
Keywords:
- AIDS-Related Complex
- Acquired Immunodeficiency Syndrome
- CD4-Positive T-Lymphocytes
- Didanosine
- Humans
- organization & administration
Other ID:
UI: 102178837
From Meeting Abstracts