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Population pharmacokinetics and simulation techniques currently play an important role in new drug development. This paper illustrates the potential value of those methods in postmarketing safety assessment, using buflomedil in elderly patients as an example. We retrospectively assessed the risk of buflomedil overdosing associated with the latest dosing recommendations of the French Drug Agency (AFSSAPS). First, buflomedil concentrations measured in 24 elderly patients were analysed with a nonparametric population approach. Then, the pharmacokinetic model was used to perform a 1000-patient Monte Carlo simulation for the two recommended buflomedil dosage regimens. The maximum concentrations calculated after 10 days of therapy were compared with levels observed in reported cases of toxicity to assess the probability of overdosing. A three-compartment model best fit concentration data. Population predictions showed little bias (-0.14 mg/L) and good precision (8.73 mg(2) /L(2)). Overall results of the simulation study showed that the application of the two recommended dosage regimens of buflomedil was associated with overdosing (C(max) > 10 mg/L) and potential toxicity in 2.9% of geriatric patients. In patients with mild renal impairment, who may receive the higher-dosage regimen by therapeutic error, the probability of overdosing was 6.2%. Despite specific dosing recommendations in case of renal impairment, this study shows that the use of buflomedil could be associated with significant risk of overdosing in geriatric patients. Such results might have enhanced decision-making when buflomedil safety was reassessed by AFSSAPS in 2006. The retrospective case of buflomedil illustrates how these methods may be valuable in postmarketing safety evaluation of potentially toxic drugs., (© 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.)

"Rave parties", all-night dance parties based on "techno" music, represent an increasing phenomenon in France. "Rave drugs" refers to a wide variety of drugs used by the young participants owing to their hallucinogenic or stimulant effects. Uncertainties about the sources of these substances, the possible contaminants and the multiplicity of the associations make it difficult to evaluate the toxic consequences that might be expected in this particular context. This report presents toxicological cases documented by analytical findings in which two pharmacological agents abused in "rave parties" in South-West of France were found. The day following a party, a 17 year-old girl showed a confused state with drowsiness and hallucinations. She confessed having consumed a white powder sold as "ecstasy", that sample analysis identified as pure ketamine. Ketamine is an anaesthetic agent primarily used in veterinary medicine and paediatrics. This drug seems to be abused, mainly by the intranasal route, owing to its hallucinogen effects. Its used in "rave-party" appears to be marked by unsuspected consumption. All long another party, a large quantity of orange tablets were sold and abused by several participants. Analysis performed on some fragments of these tablets revealed the presence of prolintane and ascorbic acid. Prolintane, an amphetamine-related substance, is a central nervous system stimulant. This compound is "freely" available in Spain in combination with several vitamins, under the form of tablets with orange coating named "Katovit" and sold at low price: 1.93 [symbol: see text]/20 tablets (200 mg of prolintane).