Concentrations of gatifloxacin in plasma and urine and penetration into prostatic and seminal fluid, ejaculate, and sperm cells after single oral administrations of 400 milligrams to volunteers.

Gatifloxacin (GTX), a new fluoroquinolone with extended antibacterial activity, is an interesting candidate for the treatment of chronic bacterial prostatitis (CBP). Besides the antibacterial spectrum, the concentrations in the target tissues and fluids are crucial for the treatment of CBP. Thus, it was of interest to investigate its penetration into prostatic and seminal fluid. GTX concentrations in plasma, urine, ejaculate, prostatic and seminal fluid, and sperm cells were determined by a high-performance liquid chromatography method after oral intake of a single 400-mg dose in 10 male Caucasian volunteers in the fasting state. Simultaneous application of the renal contrast agent iohexol was used to estimate the maximal possible contamination of ejaculate and prostatic and seminal fluid by urine. GTX was well tolerated. The means (standard deviations) for the following parameters were as indicated: time to maximum concentration of drug in serum, 1.66 (0. 91) h; maximum concentration of drug in serum, 2.90 (0.39) microg/ml; area under the concentration-time curve from 0 to 24 h, 25.65 microg. h/ml; and half life, 7.2 (0.90) h. Within 12 h about 50% of the drug was excreted unchanged into the urine. The mean renal clearance was 169 ml/min. The gatifloxacin concentrations in ejaculate, seminal fluid, and prostatic fluid were in the range of the corresponding plasma concentrations which were 1.92 (0.27) microg/ml at approximately the same time point (4 h after drug intake). The concentrations in sperm cells (0.195, 0.076, and 0.011 microg/ml) could be determined in three subjects. The good penetration into prostatic and seminal fluid, the good tolerance, and the previously reported broad antibacterial spectrum suggest that GTX may be a good alternative for the treatment of chronic bacterial prostatitis. Clinical studies should be performed to confirm this assumption.

Serum concentrations of tramadol enantiomers during patient-controlled analgesia.

AIMS: Tramadol, a centrally acting analgesic, is used as a racemate containing 50% of a (+)- and 50% of a (-)-enantiomer. This paper presents the pharmacokinetic results of postoperative patient-controlled analgesia using (+)-tramadol, (-)-tramadol or the racemate. METHODS: Ninety-eight patients recovering from major gynaecological surgery were treated in a randomised, double-blind study with (+)-tramadol, (-)-tramadol or the racemate. Following an i.v. bolus up to a maximum of 200 mg, patient-controlled analgesia with demand doses of 20 mg was made available for 24 h. Prior to each demand, the serum concentrations of the enantiomers of tramadol and its metabolite M1 were measured in 92 patients. RESULTS: The mean concentrations of tramadol during the postsurgery phase were 470+/-323 ng ml-1, 590+/-410 ng ml-1 and 771+/-451 ng ml-1 in the (+)-, racemate- and (-)-group, respectively ((+) vs (-), P<0.05); the mean concentrations of the metabolite M1 were 57+/-18 ng ml-1, 84+/-34 ng ml-1 and 96+/-41 ng ml-1 in the (+)-, racemate- and (-)-group, respectively ((+) vs (-) and (+) vs racemate, P<0.05). The mean concentrations of (+)-tramadol and (+)-M1 were lower in the racemate- than in the (+)-group (P<0.05), those of (-)-tramadol and (-)-M1 were lower in the racemate than in the (-)-group (P<0.05). In the racemate group, the mean serum concentrations of (+)-tramadol were higher than those of (-)-tramadol (P<0.05), whereas the mean serum concentrations of (-)-M1 were higher than those of (+)-M1 (P<0. 05). CONCLUSIONS: The therapeutic serum concentration of tramadol and M1 showed a great variability. The lowest mean concentrations were measured in the (+)-group and the highest in (-)-group. This is in agreement with the clinical finding that (+)-tramadol is a more potent analgesic than (-)-tramadol.

Effects of prostacyclin analogs on cyclic adenosine monophosphate and superoxide formation in human polymorphonuclear leukocytes stimulated by formyl-methionyl-leucyl-phenylalanine.

The modulation of cyclic AMP levels and superoxide release in isolated FMLP-stimulated human PMN by two oxacyclic analogs and one carbacyclic analog of PGI2 and by PGE1 is investigated over a wide range of concentrations of the test compounds. The prostacyclin analogs only marginally increase the cyclic AMP levels in unstimulated PMN but like PGE1 potentiate the FMLP-induced rise in cyclic AMP. The concentration dependency is bell-shaped with a maximum effect at about 10 microM of the prostanoids. In contrast, all prostanoids dose-dependently inhibit FMLP-induced superoxide release almost to completion. The relative inhibitory potency of the prostacyclin analogs corresponds to their prostacyclin-like action in other systems. It is therefore suggested that PMN contain prostacyclin receptors, which, however, have weaker affinities than those in platelets. The lack of correlation between inhibition of superoxide formation and modulation of the cyclic AMP system rules out the possibility that cyclic AMP can simply be considered the second messenger of prostacyclins in PMN. The potential biological relevance of the effects of prostacyclin-like compounds on PMN functions is discussed.