Troleandomycin hepatotoxicity: a case report of overt jaundice and a placebo-controlled trial.
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Adult↗
Biomedical subjects
P Nicolas
Publications and source records attributed to P Nicolas.
[Value of the theory of the optimal sampling scheme for bioequivalence studies].
Use of optimal sampling theory (OST) in pharmacokinetic studies allows a large reduction of the number of sampling times without loss in parameter estimation precision. OST has been applied to the determination of bioavailability parameters [area under the curve (AUC), maximal concentration (Cmax), time to reach maximal concentration, (Tmax)]. Three different Monte-Carlo simulations in twelve subjects have been performed, corresponding to different pharmacokinetic models: one-compartment with or without a lag time, two-compartment. Bioavailability parameters were estimated using a non-compartmental method (with 12 to 16 sampling times) and OST method (6 to 7 sampling times). Estimates were compared with true values. Bias and RMSE were similar with both methods for AUC and Cmax, while Tmax was better estimated using OST method. However, when a posteriori identifiability of the model was poor, use of a maximum a posteriori Bayesian estimator improved considerably the efficacy of OST method. Potential interest of OST for increasing statistical power of bioequivalence studies at the same cost is discussed, as well as possible limitations.
Biological Availability↗
[Control of an epidemic of meningococcal meningitis in Central Africa].
A severe epidemic of group A meningococcal disease occurred in the northwest part of the Central African Republic from January to March 1992. The outbreak affected a large and densely populated area, with a poor road network, located 400 kilometers south of the classical meningitis belt. An initial selective vaccination campaign was carried out by the national health care service. As the epidemic was continuing, the national authorities asked for international assistance. The French participated by sending Bioforce, a medical task force designed by the Ministry of Defense, with the financial support of the Ministry of Cooperation. Neisseria meningitidis strains were isolated and identified within 36 hours by the Bioforce field laboratory. Strains from 24 patients were sent to the Pasteur Institute in Paris (Neisseria Unit) for serotyping, testing of antibiotic susceptibility, and multilocus enzyme electrophoresis. With one exception, all strains had formula A:4:P1.9. By an initial rapid assessment, the limits of the affected area and populations were determined. The weekly incidence rates observed in different areas varied within a range of 3 to 10 cases per 1,000, with fatality rates from 20 to 30 cases per 100. The spread of the epidemic was stopped by a mass vaccination campaign, which targeted the entire population (200,000 immunizations) of the affected area. The case fatality rate could not be reduced below 15%, despite antimicrobial treatments implemented as soon as possible. The optimal treatment was the standard single intramuscular injection of oily chloramphenicol. The predictive values of clinical symptoms were calculated. The efficacy of vaccination was estimated by comparison of the percentage of people immunized and the proportion of those vaccinated people who developed meningitis identified during the 3 weeks following the mass vaccination campaign. The efficacy varied between 93 to 95% according to the place. The typical weekly incidence rate of 1 case per 1,000 is not a relevant threshold to sufficiently and immediately detect a meningitis outbreak and needs to be reconsidered.
Adolescent↗