Bioavailability of ibuprofen from matrix mini-tablets based on a mixture of starch and microcrystalline wax.

The bioavailability of ibuprofen from matrix mini-tablets based on microcrystalline wax and a starch derivative was tested. An oral dose of 300 mg of ibuprofen was administered to healthy volunteers (n=8) in a randomized cross-over study design either as a commercial matrix formulation (Ibu-Slow 600) or as mini-tablets (filled into hard gelatin capsules). The mini-tablets consisted of 60% ibuprofen, 15% Paracera M (wax), 22.5% DDWM (starch) and 2.5% triacetin (lubricant). t50% of the in vitro release was 4.5 and 5 h for the mini-tablet and Ibu-slow formulations, respectively. Both formulations behaved in vivo as sustained-release formulation; their HVDt50%Cmax value was determined at 5.6 and 5.1 h for the mini-tablet and Ibu-slow formulations, respectively. A significantly higher value of Cmax was seen for the mini-tablet formulation, resulting in a relative bioavailability of 116 +/- 22.6% compared to the Ibu-slow matrix. These data demonstrate that the experimental mini-tablets can be used to formulate sustained-release dosage forms.

Effects of smoking, CYP2D6 genotype, and concomitant drug intake on the steady state plasma concentrations of haloperidol and reduced haloperidol in schizophrenic inpatients.

The effects of smoking, CYP2D6 genotype, and concomitant use of enzyme inducers or inhibitors on the steady state plasma concentrations of haloperidol (HAL) and reduced haloperidol (RHAL) were evaluated in 92 schizophrenic inpatients. All but three of these patients received concomitant medication, in many cases with drugs potentially interacting with HAL. Of the 92 patients, 63 were treated orally with HAL in a daily dose of 0.4 to 50 mg; 29 patients were treated intramuscularly with a daily equivalent dose of HAL decanoate (expressed as HAL) of 1.8 to 17.9 mg. A wide interindividual variation in HAL dose and in steady state plasma concentrations of HAL and RHAL was observed. In the patients treated orally, the daily oral dose was about 4 times higher and the dose-normalized HAL (but not RHAL) plasma concentrations were significantly lower in smokers (n = 40) than in nonsmokers (n = 23) (p < 0.01). The dose-normalized RHAL (but not HAL) plasma concentrations and the RHAL/HAL ratio were significantly higher in poor metabolizers (PMs) than in extensive metabolizers (EMs). There was a trend toward an effect of potentially interacting drugs (inducers or inhibitors) on dose, dose-normalized HAL and RHAL plasma concentrations, and the RHAL/HAL ratio. In the patients treated intramuscularly, the dose-normalized HAL (but not RHAL) plasma concentrations were significantly lower in smokers than in nonsmokers, but no differences in doses were observed. This naturalistic study of modest sample size in a polymedicated population shows an effect of smoking and CYP2D6 genotype (and to a lesser extent, of interacting drugs) on the kinetics of HAL.

A prospective study in healthy volunteers of the topical absorption of a 5% rifaximin cream.

Rifaximin, the active ingredient of an antibiotic cream, is a synthetic antibiotic derived from rifamycin and characterized by minimal absorption. In animals, no absorption was detected after topical application on the skin. The question as to whether there is detectable absorption in man by the same administration route is answered by this study in healthy volunteers. One gram of the cream containing 5% rifaximin was massaged on a sizable surface of skin prepared prior to application by mechanical abrasion. Rifaximin concentrations in blood and urine were then determined by means of HPLC-electrochemical-coulometrical detection. Concentrations in all samples being less than 2.5 ng/ml, the method's limit of detection, it is concluded that there is no detectable absorption in man. No adverse reactions were reported during this one day study. The results confirm studies performed in animals which showed that rifaximin is not absorbed and is well tolerated.