Determination of dosing guidelines for stavudine (2 ',3 '-didehydro-3 '-deoxythymidine) in children with human immunodeficiency virus infection

The results of the development of dosing guidelines for stavudine in human immunodeficiency virus (HIV)-infected children are summarized. Included in the integrated analyses were 21 and 33 HIV-infected pediatric and adult pat ients, respectively, from three phase I-II studies. Data for 21 children an d 18 adults who received intravenous doses of 0.125 to 2 and 0.5 to 1 mg/kg of body weight, respectively, were used for the determination of dosing gu idelines; exposure data for 16 children and 15 adults who received oral dos es of I to 2 and 0.5 to 1 mg/kg/day, respectively, were used to validate th e dosing recommendations for children. Significant relationships were obser ved between total body clearance (in milliliters per minute) in children an d adults combined and demographic parameters of age, body weight, and body surface area (R-2 = 0.77 to 0.80; P = 0.0001), Models of approximated pedia tric dose based on clearance values and direct adult exposure yielded a sta vudine dosage of 2 mg/kg/day for children of less than or equal to 30 kg of body weight and 1 mg/kg/day (adult dose) for children of >30 kg of body we ight.