ZALCITABINE POPULATION PHARMACOKINETICS - APPLICATION OF RADIOIMMUNOASSAY

Zalcitabine population pharmacokinetics were evaluated in 44 human imm unodeficiency virus-infected patients (39 males and 5 females) in our immunodeficiency clinic, Eighty-one blood samples were collected durin g routine clinic visits for the measurement of plasma zalcitabine conc entrations by radioimmunoassay (1.84 +/- 1.24 samples/patient; range, 1 to 6 samples/patient). These data, along with dosing information, ag e (38.6 +/- 7.13 years), sex, weight (79.1 +/- 15.0 kg), and estimated creatinine clearance (89.1 +/- 21.5 ml/min), were entered into NONMEM to obtain population estimates for zalcitabine pharmacokinetic parame ters (4). The standard curve of the radioimmunoassay ranged from 0.5 t o 50.0 ng/ml, The observed concentrations of zalcitabine in plasma ran ged from 2.01 to 8.57 ng/ml following the administration of doses of e ither 0.375 or 0.75 mg, A one-compartment model best fit the data, The addition of patient covariates did not improve the basic fit of the m odel to the data. Oral clearance was determined to be 14.8 liters/h (0 .19 liter/h/kg; coefficient of variation [CV] = 23.8%), while the volu me of distribution was estimated to be 87.6 liters (1.18 liters/kg; CV = 54.0%), We were also able to obtain individual estimates of oral cl earance (range, 8.05 to 19.8 liters/h; 0.11 to 0.30 liter/h/kg) and vo lume of distribution (range, 49.2 to 161 liters; 0.43 to 1.92 liters/k g) of zalcitabine in these patients with the POSTHOC option in NONMEM, Our value for oral clearance agrees well with other estimates of oral clearance from traditional pharmacokinetic studies of zalcitabine and suggests that population methods may be a reasonable alternative to t hese traditional approaches for obtaining information on the dispositi on of zalcitabine.