Biomedical subjects

I A Taha

Publications and source records attributed to I A Taha.

3 recordsLinked to original sources

PubMed1983

Pharmacokinetics of melphalan in children following high-dose intravenous injection.

The pharmacokinetics of high-dose IV melphalan (140 or 220 mg m-2) were studied after 12 administrations in 10 children (aged 2.5-16 years) undergoing chemotherapy for either neuroblastoma or Ewing's tumour. To assess whether a simpler and less expensive nitrobenzylpyridine (NBP) spectrophotometric assay for alkylating activity was a satisfactory alternative to high-pressure liquid chromatography (HPLC), the plasma melphalan concentration was estimated by both methods in five cases. Analysis of the disposition of melphalan gave a mean half-life of 1.3 +/- 1.0 (SD) h, clearance 18.4 +/- 9.4 l X h-1 X m-2, and apparent volume of distribution 26.3 +/- 18.0 l X m-2. These pharmacokinetic parameters were similar to those found in adults: no correlation was found between any parameter and age or glomerular filtration rate. NBP alkylating activity determinations yielded consistent results and good correlation with plasma melphalan concentration. However, concordance analysis indicated a consistent bias, the NBP assay always giving lower estimates of plasma melphalan concentration: HPLC assay therefore remains the method of choice for determining plasma melphalan pharmacokinetics.

Adolescent↗

PubMed1982

Plasma melphalan and prednisolone concentrations during oral therapy for multiple myeloma.

Nine patients with myeloma were studied over 13 oral administrations of 10 mg melphalan and 5-10 mg prednisolone. Plasma melphalan concentrations were estimated by high-pressure liquid chromatography, prednisolone concentrations by quantitative thin-layer chromatography. The mean plasma half-life of unchanged melphalan was 0.9 +/- 0.5 (SD) h. The 'lag-time' before melphalan was detected in the plasma varied from 1 to 4 h, the mean peak concentration was 96 +/- 21 ng/ml, and the mean area under the plasma concentration by time curve was 160 +/- 78 ng h/ml. This variability was consistent with observations made elsewhere following much higher oral doses of melphalan and illustrates the relatively wide interindividual variability of absorption. Observations made in the same subjects on two separate occasions showed lower variability. The melphalan elimination rate was not significantly affected by moderate impairment of creatinine clearance (to 31 ml/min). Absorption of prednisolone in five of these patients was apparently normal and unaffected by concurrent administration of melphalan.

Adult↗

PubMed1981

Melphalan estimation by quantitative thin-layer chromatography. Observations on melphalan hydrolysis in vitro and pharmacokinetics in rabbits.

A simple and specific quantitative high-performance thin-layer chromatographic (HPTLC) assay for melphalan in plasma is described. This assay was linear over the investigated range of 50--3,000 ng/ml, with a minimum level of detection of 20 ng/ml. Comparison with a high-pressure liquid chromatographic (HPLC) technique yielded similar estimates for melphalan concentrations in human plasma samples. The HPTLC method, unlike the HPLC technique, does not resolve monohydroxymelphalan satisfactorily. The HPTLC method was used to determine the activation energy for in vitro melphalan hydrolysis: this was 14.5 kcal/mole. The pharmacokinetics of melphalan in rabbits were also investigated. The mean t1/2 in four animals was 32.6 +/- 10.3 (S.D.) min and following IV administration to two animals the apparent volumes of distribution were 2.20 and 1.73 l/kg.

Animals↗