Background/Aims: Absorption, biotransformation and elimination of safinamide, an enantiomeric α-aminoamide derivative developed as an add-on therapy for Parkinson's disease patients, were studied in healthy volunteers administered a single oral dose of 400 mg ¹⁴C safinamide methanesulphonate, labelled in metabolically stable positions. Methods: Pharmacokinetics of the parent compound were investigated up to 96 h, of ¹⁴C radioactivity up to 192/200 h post-dose. Results/Conclusions: Maximum concentration was achieved at 1 h (plasma, median T_max) for parent drug and at 7 and 1.5 h for plasma and whole blood ¹⁴C radioactivity, respectively. Terminal half-lives were about 22 h for unchanged safinamide and 80 h for radioactivity. Safinamide deaminated acid and the N-dealkylated acid were identified as major metabolites in urine and plasma. In urine, the β-glucuronide of the N-dealkylated acid and the monohydroxy safinamide were also characterized. In addition, the glycine conjugate of the N-dealkylated acid and 2-[4-hydroxybenzylamino]propanamide were tentatively identified as minor urinary metabolites.

The interaction between the main components of the new glycopeptide antibiotic teicoplanin, A2-2, A2-3, A2-4, A2-5 and A3-1, and human serum albumin has been studied in vitro by equilibrium dialysis (pH 7.4, 37 degrees C). From Scatchard analysis of the data, the calculated association constants (Ka) were: A2-2, 2.47 X 10(4), A2-3, 2.86 X 10(4), A2-4, 2.95 X 10(4) and A2-5, 3.87 X 10(4) mol.l-1. The number of binding sites per albumin molecule ranged between 1.23 to 1.31. A3-1 had a lower affinity with a Ka of about 5 X 10(3) mol.l-1. Extrapolated to the in vivo situation, the data suggested that about 90-95% of A2 components will be bound to serum albumin, and about 68-72% of A3-1. The in vitro findings were confirmed by a pharmacokinetic study in volunteers given [14C] teicoplanin i.v., in whom the fraction of teicoplanin bound to serum protein ranged between 87.6 and 90.8%.

A study on the pharmacokinetics of rifapentine, a new long-lasting rifamycin, has been carried out in the rat, the mouse and the rabbit. The investigation was made using either radioactive or unlabelled rifapentine and both the total -=C and the unchanged compound were assayed.In the rat, the overall evidence obtained was: (a) the oral absorption of rifapentine into central compartment, due to its poor water solubility, appears to be dose-dependent with a satisfactory oral absorption (84°0) after a dose of 3 mg/kg, lower (65%) after 10 mg/kg; (b) the antibiotic undergoes rapid liver uptake while it diffuses into the tissue compartment more slowly, with particular affinity for the adrenals, pancreas and kidneys; concentrations higher than in plasma were also measured in the lungs; (c) elimination of rifapentine from the blood and tissue compartments suggests a non linear capacity-limited kinetics where the terminal elimination phase has monoexponential course. Terminal plasma half-life ranged between 14 and 18 hours: (d) the compound is eliminated mainly via the bile with the feces (92% of dose).In mice rifapentine shows a kinetic profile resembling that obtained in rats, whereas in rabbits is metabolized and or eliminated much more rapidly with a half-life of only 1.8 hours.Rifapentine (INN), Fig.

The pharmacokinetic profile of [14C]teicoplanin was studied in male Sprague-Dawley rats given a single 10,000-U/kg intravenous dose. The disposition of the antimicrobial activity in the body was estimated by a three-compartment open model. Plasma concentration data were fitted to a three-exponent equation. The profile of total 14C in plasma was similar to that of the microbiological activity. The cumulative recovery of total 14C 5 days after drug administration averaged 76.3% of the administered dose in the urine and 8.7% in the feces. The residual dose remaining in the animal carcasses was 11.1%. Teicoplanin was widely distributed in the body. In almost all organs, the maximum concentration of [14C]teicoplanin was already reached at the first time of killing, which was 0.25 h after the administration of drug. The liver, kidneys, skin, and fat contained most of the residual dose found in the animal carcasses 120 h after administration and behaved as a deep compartment with the adrenal glands and spleen.

The new oral 200-mg rifamycin SV MMX modified-release tablets, designed to deliver rifamycin SV directly into the colonic lumen, offer considerable advantages over the existing immediate-release antidiarrheic formulations. In two pharmacokinetics studies of healthy volunteers, the absorption, urinary excretion, and fecal elimination of rifamycin SV after single-and multiple-dose regimens of the new formulation were investigated. Concentrations in plasma of >2 ng/ml were infrequently and randomly quantifiable after single and multiple oral doses. The systemic exposure to rifamycin SV after single and multiple oral doses of MMX tablets under fasting and fed conditions or following a four-times-a-day (q.i.d.) or a twice-a-day (b.i.d.) regimen could be considered negligible. With both oral regimens, the drug was confirmed to be very poorly absorbable systemically. The amount of systemically absorbed antibiotic excreted by the renal route is far lower than 0.01% of the administered dose after both the single-and multiple-dose regimens. The absolute bioavailability, calculated as the mean percent ratio between total urinary excretion amounts (⌺Xu) after a single intravenous injection and after a single oral dose under fasting conditions, was 0.0410 ؎ 0.0617. The total elimination of the unchanged rifamycin SV with feces was 87% of the administered oral dose. No significant effect of rifamycin SV on vital signs, electrocardiograms, or laboratory parameters was observed.