[Hospital pharmaceutical practice in prison]. / L'exercice pharmaceutique hospitalier en milieu carcéral.

SUMMARY: Since 1994, hospital pharmaceutical teams have been in charge of pharmaceutical tasks in "unités de consultation et de soins ambulatoires" (UCSA), which are hospital consulting care units in French prisons. In 2008, pharmaceutical team in Parisian prisons received 6500 prescriptions and prepared 85,000 nominative bags containing drugs. Prisoners were 1.3% to receive treatments against HIV, 8.2% cardiovascular drugs, 7.2% opioid substitution treatments, and 52.9% psychoactive drugs, including 39.3% hypnotics, 40.5% anxiolytics, 11.3% antidepressants and 12.2% neuroleptics. In prison, the dichotomy between somatic and mental care is marked, attitudes of prisoners about their medicines are complex (important claims, embezzlement, etc.) and it is difficult for law defendants to maintain treatment confidentiality and to prepare prison outing in terms of health. To attenuate the heterogeneity of drug distribution systems in French prisons, we propose pharmaceutical analysis of prescriptions and nominative dispensation, computerization in UCSA in coordination with hospitals, a better contribution of prison medical and pharmaceutical staff in hospital "drug committees" and the redaction of pharmaceutical guidelines. Acting in concert with multidisciplinary medical staff in UCSA, pharmaceutical teams have to develop epidemiological studies to improve knowledge in prisoner's health and also prevention and health care in prison.

Validation of an HPLC-UV method for sorafenib determination in human plasma and application to cancer patients in routine clinical practice.

Sorafenib, a new oral multikinase inhibitor with antiangiogenic properties, has demonstrated preclinical and clinical activity against several tumor types. The aims of this study were to validate a method for the measurement of sorafenib in plasma from cancer patients, then to test this method in clinical practice. Following liquid-liquid extraction, the compounds were separated with gradient elution (on a C18 ultrasphere ODS column using a mobile phase of acetonitrile/20 mM ammonium acetate), then detected at 255 nm. The calibration was linear in the range 0.5-20 mg/L. Intra- and inter-assay precision was lower than 7 and 10%, respectively, at 0.5, 3 and 20 mg/L. Plasma sorafenib concentrations were measured in 22 cancer patients (99 samples). The mean trough sorafenib concentration (C(min)) and concentration at peak were 4.3+/-2.5 mg/L (n=68, CV=57.5%) and 6.2+/-3.0 mg/L (n=31, CV=47.5%), respectively. Mean sorafenib C(min) in eight patients who experienced grade 3 drug-related adverse events was approximately 1.5-fold greater than that observed in the remaining patients (7.7+/-3.6 mg/L vs. 4.4+/-2.4 mg/L, P=0.0083). In conclusion, the method was successfully used in routine practice to monitor plasma concentrations of sorafenib in cancer patients. Finally, large interindividual variability and higher exposure in patients experiencing severe toxicity support the need for therapeutic drug monitoring to ensure an optimal exposure to sorafenib.

[Tobacco reduction in a prison of France]. / La réduction tabagique à la maison d'arrêt de Paris-La Santé

SUBJECT: Little is known about free nicotine transdermal patch efficacy on tobacco reduction in prisoners. The objective is to study this efficacy in prison as well as motivations to reduce and influence of socioeconomic conditions and other addictions in prisoners' aspiration to stop smoking. METHODS: A prospective study was proposed to prisoners candidate to tobacco cessation. Assessment was made by questionnaires and visits to physicians working at the prison. Nicotinic patches were systematically proposed to patients with a starting 15 mg/16 h dose (or 10 mg/16 h if the dependence was low), followed by a 10 and 5 mg/16 h dose reduction. RESULTS: Prisoners motivated to smoking cessation (N=73) generally had multiaddictive behaviours and precarious socioeconomic profile. Thirty percent of prisoners self-reported a reduction of 50% of their cigarettes consumption until they left prison. Median duration of this successful treatment was 45 days. Median duration of treatment response for patients who relapsed in prison (15 %) was 75 days. No predictive factor of success was found. CONCLUSION: Tobacco reduction is possible in prison even if living conditions are not favourable.

Increased intestinal absorption of cefixime by nifedipine in the rat intestinal perfusion model: evidence for a neural regulation.

In healthy volunteers, the simultaneous administration of nifedipine and cefixime has been shown to increase the oral absorption of the antibiotic. To investigate the pharmacological basis of this interaction, we used an in situ intestinal perfusion technique in the rat. pH 5.5 yielded optimum cefixime absorption, which was greater in segments from the duodenojejunum than in those from the jejunoileum. Cefixime absorption was similar when perfused at 0.5 and 1.0 mg/ml, suggesting transport saturation at the lower concentration. Cefixime arterial and portal blood concentrations after an intestinal perfusion of 0.5 mg/ml cefixime were significantly increased by a previous 15-min intestinal perfusion of 0.05 mg/ml nifedipine. Nifedipine did not significantly alter intestinal blood flow. At the end of the cefixime perfusion, intestinal blood flow was higher in the nifedipine group than in the control group (0.44 +/- 0.12 vs. 0.26 +/- 0.09 ml.min-1.g of intestine wt-1, respectively), although the difference did not reach statistical significance. The absorption kinetics of salicylic acid, which is strictly absorbed by passive diffusion, were unaffected by nifedipine. After 15 and 50 min of recirculation, residual salicylate levels fell from 85.1 +/- 5.6% to 57.1 +/- 2.8% with nifedipine compared with 87.4 +/- 1.4% to 52.8 +/- 1.6% without nifedipine. Thus, the improvement in cefixime absorption by nifedipine was not secondary to increased local blood flows or to induced passive diffusion mechanisms. Nifedipine did not affect intestinal motility. The action of nifedipine appears to indirect, involving a neural regulation, because any increase in cefixime absorption was prevented by tetrodotoxin and hexamethonium administration.

High-performance liquid chromatographic method for the determination of cefpodoxime levels in plasma and sinus mucosa.

A selective HPLC method is described for the determination of cefpodoxime levels in plasma and sinus mucosa. Sample preparation included solid-phase extraction with a C8 cartridge. Cefpodoxime and cefaclor (internal standard) were eluted with methanol and analyzed on an optimised system consisting of a C18 stationary phase and a ternary mobile phase (0.05 M acetate buffer pH 3.8-methanol-acetonitrile, 87:103, v/v) monitored at 235 nm. Linearity and both between- and within-day reproducibility were assessed for plasma and sinus mucosa samples. Inter-assay coefficients of variation were lower than 13.6% (n = 10) for plasma (0.2 micrograms/ml) and lower than 12.4% (n = 5) for sinus mucosa (0.25 micrograms/g). The quantification limit was 0.05 micrograms/ml for plasma and 0.13 micrograms/g for tissue. The method was used to study the diffusion of cefpodoxime in sinus mucosa.

Efficacy of continuous zidovudine infusion at early stages of retroviral infection in mice.

We studied the pharmacokinetics of zidovudine (ZDV) in mice after twice-daily s.c. bolus injections and during continuous infusion with s.c. ALZET mini-osmotic pumps. We also compared the antiretroviral efficacy of these two modes of administration against Friend leukemia virus (FLV) infection. Mice were infected by retro-orbital inoculation of about 50 focus-forming units (ffu) of FLV, and treatment was started 1 or 4 h later with ZDV at 40 mg/kg/day for 5 days. Efficacy was evaluated in terms of spleen weight and/or virus titer (spleen focus assay) on day 21 in comparison with untreated infected mice. In a separate experiment, survival time after infection was also monitored over a 140-day period. Plasma concentrations of ZDV were determined by means of high-performance liquid chromatography. Following bolus administration, the peak plasma ZDV concentration (30.5 mg/ml) was reached within 10 min, and elimination was rapid (mean half-life, 0.7 h). During the continuous infusion, the mean concentration was constant at about 1.2 mg/ml. After 5 days of treatment, continuous ZDV infusion consistently inhibited virus-induced splenomegaly by more than 97%; bolus injections were less effective with inhibition ranging from 13 to 98%. These results suggest that moderate constant levels of ZDV have greater antiretroviral efficacy than intermittent high concentrations.