Pharmacokinetics and safety of prochlorperazine in paediatric patients receiving cancer chemotherapy.
Nausea and vomiting are common clinical problems in patients receiving cancer chemotherapy. Metoclopramide is often used but frequently causes extrapyramidal reactions. As an alternative, prochlorperazine is prescribed but no data on its pharmacokinetics in paediatric patients are available to guide the choice of suitable dosages. The primary objective of this study was to evaluate the pharmacokinetics and safety of intravenous prochlorperazine in paediatric patients receiving cancer chemotherapy. Eleven patients (ages 1-9 years) who received high doses of cisplatin or cyclophosphamide were given three to four intermittent doses of 0.2 mg/kg prochlorperazine i.v. over a period of 6-9 h. Multiple blood samples were collected and prochlorperazine was quantified by a specific gas-liquid chromatographic method. The peak serum concentrations ranged from 402 to 5,608 ng/ml. The total clearance and elimination half-life ranged from 0.03 to 0.28 (mean: 0.12) litre/kg/h, and from 1.2 to 15.5 (mean: 5.6) h, respectively. No adverse effects were observed in our patients. Three patients had uncontrolled episodes of vomiting during prochlorperazine therapy. These data suggest: (i) that there was a substantial interpatient variability in prochlorperazine pharmacokinetics thus the dose requirement differed among patients; and (ii) that prochlorperazine appeared safe at the doses used but higher doses may be required to control nausea and vomiting in some paediatric patients receiving high-dose cisplatin or cyclophosphamide therapy.
Nahata
M C
MC
College of Pharmacy, Ohio State University, Columbus 43210.
Ford
C
C
Ruymann
F B
FB
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects; D003520:Cyclophosphamide / Q000009:adverse effects; D006801:Humans; D007223:Infant; D009369:Neoplasms / Q000188:drug therapy*; D011346:Prochlorperazine / Q000009:adverse effects / Q000493:pharmacokinetics*; D014839:Vomiting / Q000517:prevention & control*
D003520:Cyclophosphamide; D002945:Cisplatin; D011346:Prochlorperazine