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Zalcitabine population pharmacokinetics: application of radioimmunoassay
J M Adams1, M J Shelton, R G Hewitt
1Department of Pharmacy Practice, State University of New York at Buffalo, Amherst 14260, USA.
Insights
Population pharmacokinetics of zalcitabine were studied in HIV patients. Population methods using NONMEM provided reliable estimates for oral clearance and volume of distribution, comparable to traditional studies.
Area of Science:
- Pharmacokinetics
- HIV/AIDS Research
- Clinical Pharmacology
Background:
- Zalcitabine is an antiretroviral medication used in HIV treatment.
- Understanding zalcitabine pharmacokinetics is crucial for optimizing patient dosing and treatment efficacy.
- Traditional pharmacokinetic studies can be resource-intensive.
Purpose of the Study:
- To evaluate the population pharmacokinetics of zalcitabine in HIV-infected patients.
- To assess the utility of population pharmacokinetic modeling as an alternative to traditional methods.
- To determine key pharmacokinetic parameters like oral clearance and volume of distribution.
Main Methods:
- Analysis of 81 plasma samples from 44 HIV-infected patients using radioimmunoassay.
- Application of NONMEM software for population pharmacokinetic modeling.
- Inclusion of demographic and clinical data (age, weight, creatinine clearance) as covariates.
Main Results:
- A one-compartment model provided the best fit for the data.
- Population oral clearance was estimated at 14.8 L/h (0.19 L/h/kg) with a CV of 23.8%.
- Population volume of distribution was estimated at 87.6 L (1.18 L/kg) with a CV of 54.0%.
Conclusions:
- Population pharmacokinetic modeling using NONMEM is a viable alternative to traditional methods for zalcitabine disposition.
- The estimated oral clearance aligns well with previous study findings.
- Individual pharmacokinetic parameters could be estimated, offering personalized insights.
Abstract:
Zalcitabine population pharmacokinetics were evaluated in 44 human immunodeficiency virus-infected patients (39 males and 5 females) in our immunodeficiency clinic. Eighty-one blood samples were collected during routine clinic visits for the measurement of plasma zalcitabine concentrations by radioimmunoassay (1.84+/-1.24 samples/patient; range, 1 to 6 samples/patient). These data, along with dosing information, age (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 parameters. The standard curve of the radioimmunoassay ranged from 0.5 to 50.0 ng/ml. The observed concentrations of zalcitabine in plasma ranged from 2.01 to 8.57 ng/ml following the administration of doses of either 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 model 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 volume 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 clearance (range, 8.05 to 19.8 liters/h; 0.11 to 0.30 liter/h/kg) and volume of distribution (range, 49.2 to 161 liters; 0.43 to 1.92 liters/kg) 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 these traditional approaches for obtaining information on the disposition of zalcitabine.