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In order to evaluate the pharmacokinetics of cyclosporine A comparing the traditional (CsA-SCG) with the microemulsion formulation (CsA-ME), 20 clinically stable heart-transplant patients were enrolled in the study. All patients were on a thrice-daily dosage regimen (mean single dose 1.14±0.4 mg kg-1 body weight) of CsA-SCG. The steady-state area under the concentration-time curve during a dosage interval was calculated during three sequential periods: (1) the first after the morning oral dose of CsA-SCG; (2) the second (8 days later) after 2 hours intravenous infusion of cyclosporine; (3) the third after the CsA-ME morning oral dose (30 days after the milligram-to-milligram dose conversion). After switching from standard formulation CsA-SCG to CsA-ME, significant changes were observed in Cmax/ss (732 ± 178 vs 935 ± 250 ng ml-1, P < 0.001) and tmax (2.63 ± 1.21 vs 1.36 ± 0.49 h, P < 0.001). The CsA-ME mean bioavailability was higher than CsA-SCG (75 ± 19 vs 66 ± 16%; P < 0.001). The main CsA pharmacokinetic parameters of both formulations in clinically stable heart-transplant patients presented evident differences from data obtained in other transplant-patient populations. © 2001 Academic Press.

Since motor fluctuations in Parkinsonian patients might be, at least in part, explained by an antagonism between levodopa (LD) and its metabolite 3-O-methyldopa (3-OMD) at blood-brain-barrier (BBB), we decided to study LD and 3-OMD plasma and cerebrospinal fluid (CSF) levels in subjects undergoing lumbar puncture for diagnostic purposes. After informed consent, 70 subjects took a tablet of carbidopa-levodopa association (Sinemet or Sinemet-CR) 0.5, 1, 2, 4, 8, 12h before blood and lumbar cerebrospinal fluid collection. LD and 3-OMD were determined by an HPLC-electrochemical method. The subjects treated with Sinemet-CR had lower LD cerebrospinal fluid concentrations along with lower LD and higher 3-OMD plasma concentrations. This pattern of LD cerebrospinal fluid concentrations may be explained by means of a transport competition between LD and 3-OMD at blood brain barrier level.

The Bayesian method (BM) can use previous information for the optimization of dosage regimen. However, Bayes' law remains true when the parameters are obtained from the infinite population. Therefore a bias might exist in the previous information and affect BM predictive performance. To overcome this shortcoming, the blood drug concentration of a patient can be used to individualize his pharmacokinetic parameters. Until now, at least two sampling strategies, i.e. steady-state and non-steady-state sampling strategies, have been developed to individualize and predict blood drug concentration. In the present study we used five sampling strategies: (1) all samples; (2) post-infusion samples; (3) during-infusion samples; (4) samples within 95% confidence interval/interquartile range of a steady-state concentration; (5) the sample of the mean/median at the mid-time-point of a steady-state to individualize and predict blood cyclosporine concentrations in haematological patients with multidrug resistance. We investigated the effects of different sampling strategies on BM and the nonlinear least squared method (NLLSM) predictive performances. The results showed that BM predictive performance was better than NLLSM. But the results did not prove that the steady-state sampling strategies were superior to the non-steady-state ones. © 1995 The Italian Pharmacological Society.