In some situations, it is preferable to use concentrations with values below the LOQ to evaluate the results of pharmacokinetic studies. However, this should not be the rule, especially when this does not bring any additional information, or when it is possible to increase the sensitivity of the bioanalytical assay.
1. The influence of spiramycin coadministration on cyclosporin pharmacokinetics was studied in five renal transplant patients. The plasma concentrations of cyclosporin were measured both by non‐specific radioimmunoassay (RIA) and high‐performance liquid chromatography (h.p.l.c.). 2. The kinetics of cyclosporin were followed before treatment, and after 1 day and then 2 weeks of oral treatment with spiramycin (3 X 10(6) iu, twice daily). The main pharmacokinetic parameters (the area under the plasma drug concentration‐time curve, the maximum plasma drug concentration and the time to reach it) obtained both by RIA and h.p.l.c. were not modified by spiramycin cotreatment after 1 day, nor after 2 weeks of spiramycin administration. Therefore, the pharmacokinetics of cyclosporin (parent drug and parent drug plus metabolites) are not influenced by the coadministration of spiramycin macrolide at therapeutic dosage. 3. Spiramycin may be preferable to other macrolide antibiotics known to interact with cyclosporin such as erythromycin or josamycin.
A radioreceptor assay for the determination of nicardipine in human serum using the active enantiomer 3H(+)PN 200-110 as radioligand is described. The assay is simple to perform, of low cost and requires only a small volume of serum. The standard curve permits measurements in the range 2.5 to 320 nM nicardipine (i.e. 1.2 to 153 ng/ml). The precision and the reproducibility of the method, evaluated from two different concentrations: 120 and 12 nM, show coefficients of variation for within and between assays, of 6% and 15% and 6% and 9%, respectively. Concentrations of nicardipine from 3 ng/ml could be measured with a satisfactory precision. The performances of the method permit the determination of nicardipine concentrations reached after therapeutic administration. Other dihydropyridine calcium channel antagonists may be measured using this assay if these compounds are used to generate the standard curves.
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