Pharmacokinetic parameters and interpatient variability is assessed in 80 febrile granulocytopenic cancer patients being treated with a third generation cephalosporin-ceftazidime. Disposition in this population appears to be significantly different than that observed in normal volunteers. Elimination half-life is prolonged by almost 50-60% in these patients. Overall treatment success in the study, with ceftazidime alone was 80% and exceeded 90% on the addition of an antigungal agent. Significant variability (60-85%) in drug disposition was observed in these patients due to an underlying disease. Although the hybrid elimination rate appears to be normally distributed, both total systemic clearance and distribution volumes reveal skewed distributions. Statistical analysis suggests that distribution of these parameters in this population may be log-normal and hence may necessitate drug monitoring to optimize drug dosage in an attempt to minimize both the toxicity and patient cost.
