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C M Eeltink

Publications and source records attributed to C M Eeltink.

5 recordsLinked to original sources
PubMed1997

Pharmacokinetics of amifostine and its metabolites in patients.

The pharmacokinetics of the cytoprotective agent amifostine (EthyolR; WR 2721) and its main metabolites (WR 1065 and the disulphides) were studied in patients participating in two phase I trials concerning carboplatin or cisplatin in combination with amifostine. Patients were treated with a single dose or three doses of amifostine (740 or 910 mg/m2). The single or first dose was given as a 15 min i.v. infusion just before administration of the chemotherapeutic agent. The additional two infusions were administered 2 and 4 h thereafter. Amifostine was rapidly cleared from the plasma, due to, at least in part, the fast conversion into WR 1065. A biphasic decrease with a final half-life of 0.8 h was observed. The active metabolite WR 1065 was cleared from the plasma with a final half-life of 7.3 +/- 3.6 h. The short initial half-life of WR 1065 can be explained by its fast uptake in tissues and the formation of disulphides. The disulphides were cleared with a final half-life of 8.4-13.4 h and were detectable for at least 24 h after treatment. They may serve as an exchangeable pool of WR 1065. The amifostine peak values at the end of each 15 min infusion did not accumulate in the multiple dosing schedule. For WR 1065 a trend towards an increase in the peak levels was observed [C1,max: 47.5 +/- 11.9 microM, C2,max: 79.0 +/- 13.2 microM, C3,max: 84.8 +/- 15.1 microM, (n = 6)], whereas a trend towards a small decrease was observed for the peak levels of the disulphides [C1,max: 184.2 +/- 12.6 microM, C2,max: 175.0 +/- 23.7 microM, C3,max: 166.0 +/- 17.2 microM, (n = 6)]. This latter finding might suggest a saturation of the disulphide formation or a change in the uptake or elimination of WR 1065, which would result in higher WR 1065 levels in plasma and tissues, after multiple doses of amifostine.

Adult↗
PubMed1997

Pharmacokinetics of carboplatin with and without amifostine in patients with solid tumors.

We showed previously that amifostine (WR 2721; Ethyol), a protector against carboplatin-induced toxicities, changed the pharmacokinetics of carboplatin in tumor-bearing nude mice. In the present study, the influence of amifostine on the pharmacokinetics of carboplatin was studied in patients when carboplatin was given in combination with three doses of amifostine, administered just before the carboplatin infusion and 2-4 h thereafter. Compared with a control group of patients who received carboplatin alone, the patients receiving the combination had a longer final half-life of ultrafilterable platinum species [5.0 h versus 3.5 h in patients with a normal creatinine clearance (Clcr > 80 ml/min); 5.6 h versus 4.2 h in those with an impaired renal function (50 < Clcr < 80 ml/min)]. This might be caused by an influence of amifostine on the renal clearance of carboplatin as suggested by a transient increase in serum creatinine levels 24 h after treatment in the patients receiving the combination (mean +/- SD: 34.1% +/- 17.2% versus -1.8% +/- 16.5% in patients treated with carboplatin alone). The impact of these changes on the area under the concentration-time curves of the ultrafilterable platinum species was hardly noticeable in patients with a normal renal function but led to a significant increase in patients with an impaired renal function (395 +/- 59 micromol/l.h versus 280 +/- 62 micromol/l.h in patients receiving carboplatin alone). The clinical relevance of this influence is unclear, although theoretically it may result in an increase in the efficacy of carboplatin, as has been observed in tumor-bearing nude mice.

Amifostine↗
PubMed1994

Paclitaxel (Taxol) concentrations in brain tumor tissue.

BACKGROUND: Paclitaxel (Taxol) is a novel chemotherapeutic agent, active against a variety of tumors. It is not known whether the drug penetrates brain tumor tissue. PATIENTS AND METHODS: Three patients with a recurrent glioma received paclitaxel (175 mg/m2) in a 3-hour i.v. infusion prior to surgery. Paclitaxel concentrations were measured in the tumor tissue, cerebrospinal fluid, cyst fluid, plasma and, in one patient, normal brain tissue. RESULTS: Tumor tissue concentrations were in the therapeutic range in all three patients. Brain tissue concentration, however, was below the detection limit of the trial. CONCLUSIONS: These findings suggest that paclitaxel may have a place in brain tumor therapy. The low concentration in normal brain tissue, as observed in one patient, may suggest, however, that the drug does not cross the intact bloodbrain barrier.

Adult↗
PubMed1993

Maternal haemolysis, elevated liver enzymes and low platelets syndrome: specific problems in the newborn.

To evaluate the effects of maternal haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome on the fetus and neonate we retrospectively investigated the outcome of 87 pregnancies. All women showed thrombocytopenia, elevated liver enzymes and haemolysis. None of them died. Nine infants were stillborn (9.9%). Of the 82 liveborn infants, 66 were delivered by caesarean section. Median gestational age of the liveborn infants was 32.6 weeks, mean birth weight was 1576 g +/- 699 g (mean +/- SD). Of these infants, 44% were small for gestational age. Perinatal asphyxia rate was 21.6%. Nine infants died in the 1st week after birth. Complications during admission included neonatal respiratory disease (43.2%), hyperbilirubinaemia (44.7%), persistent ductus arteriosus (16.2%), thrombocytopenia (34%) and hypoglycaemia (16.2%). Artificial ventilation was necessary in 37 infants. Mean duration of admission was 51 days. HELLP syndrome is associated with poor perinatal outcome; the incidence of caesarean section is high and there is an increased risk for preterm birth and growth retardation. No specific neonatal pathology due to maternal HELLP syndrome was found.

Female↗