The myelotoxicity of carboplatin is influenced by the time of its administration.

Previous studies have demonstrated that there are circadian rhythms in susceptibility to a range of commonly used cytotoxic drugs. In this study we have compared the pharmacokinetics and myelotoxicity of carboplatin administered at 18.00 and 06.00 in random order in patients with advanced ovarian carcinoma. Carboplatin treatment at 06.00 is associated with significantly greater thrombocytopenia than at 18.00 (platelet nadir 95,000 versus 180,000, p less than 0.05). There was no pharmacokinetic difference in the patients' handling of ultrafilterable platinum therefore it is possible that there is an intrinsic rhythm of susceptibility of bone marrow to carboplatin.

Pharmacokinetics of cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV (iproplatinum, CHIP) in patients with normal and impaired renal function and following intraperitoneal administration.

CHIP is a quadrivalent platinum (Pt) complex, introduced clinically as a less toxic alternative to cis-platinum. The drug's major route of excretion is via the kidneys, and in this study the pharmacokinetics of unchanged CHIP, filterable Pt and total Pt have been determined following intravenous administration to patients with a range of renal function. Total Pt and filterable Pt in plasma decayed biexponentially and was fitted to a two-compartment model, whereas unchanged CHIP declined monoexponentially and was best fitted to a one-compartment model, according to Akaike's information criteria. There is a correlation between the unchanged CHIP clearance and 51Cr-EDTA clearance. The pharmacokinetics of CHIP was determined following intraperitoneal (i.p.) administration (dose, 150-300 mg m-2 4 h dwell time) and a regional advantage (peritoneal peak concentration/plasma peak concentration) of approximately 30 fold was seen. It is likely that the dose of CHIP will need to be reduced in patients with impaired renal function, and the use of i.p. CHIP in ovarian carcinoma warrants further study.

The analysis and animal pharmacokinetics of 1,2,4, triglycidyl urazol using a high-pressure liquid chromatographic technique.

This article details a procedure for the analysis of TGU by a simple high-pressure liquid chromatographic (HPLC) method. Linearity is maintained over the range from zero to at least 30 micrograms 1,2,4, triglycidyl urazol (TGU). The sensitivity of the assay is 250 ng/ml. A second peak, as yet unidentified, was detected on the chromatogram and probably represents a metabolite of TGU. The pharmacokinetic profile of TGU in Porton mice shows a first-order elimination process with a half-life (t1/2 alpha) of 1.5 min for the distribution phase and a t1/2 beta of 5 min. The apparent volume of distribution is 0.75 ml and the clearance 0.10 ml/min with a elimination rate constant of 0.14 min.