In 11 neurosurgical patients (seven women, four men, aged 22-73 years) undergoing external ventriculostomy, serum and cerebrospinal fluid (CSF) pharmacokinetics of ceftazidime (CAZ) administered as a chemoprophylactic agent were evaluated. Concentrations of CAZ in CSF correlated significantly (p less than 0.05) with serum concentrations and with leucocyte counts in CSF. Peak concentrations in CSF (range 0-25.5 mg/l) exceeded the MIC90 of Staphylococcus species in two and of Pseudomonas and Enterobacter species in five of 11 patients. The MIC90 values of the other relevant bacteria causing CNS infections in these patients were surpassed in nine of 11 patients.

Adult↗

PubMedDate not supplied

Effects of oxotremorine after nigrostriatal lesions in rats.

Bilateral injection of 6-hydroxy-dopamine (6-OH-DA) (8mug/4mul) into the substantia nigra causes a significant decrease of the dopamine content in the nucleus caudatus. The intraventricular application of 6-OH-DA (250 mug/10 mul) induces a considerable decrease of dopamine in the caudate nucleus as well as in the globus pallidus and in the medial septal region. Simultaneous changes in norepinephrine content are less spezific. It has to be assumed that there are dopaminergic nerve endings in the glubus pallidus not originating in the substantia nigra. Only after intraventricular applications of 6-OH-DA s short-term and reversible reduction of oxotremorin-induced tremor has been observed. Lesions of the nigrostriatal pathway cause an impairment of motility, probably elicited by rigidity and akinesia. These symptoms correlate better than the tremor to biochemical changes following nigro-striatal pathway lesions.

Animals↗

PubMedDate not supplied

Quinolone inhibition of cytochrome P-450-dependent caffeine metabolism in human liver microsomes.

Inhibitory effects of the quinolone antibiotics ofloxacin, lomefloxacin, pipemidic acid, ciprofloxacin, and enoxacin on caffeine metabolism were examined in vitro with human liver microsomes of four donors. All drugs competitively inhibited the activity of 3-demethylation, the major pathway of caffeine metabolism. Enoxacin, ciprofloxacin, and pipemidic acid were strong inhibitors exhibiting Ki values between 0.1 and 0.2 mM. Lomefloxacin and ofloxacin had moderate effects with Ki values of 1.2 and 3.6 mM, respectively. The rate of caffeine 7-demethylation (which amounted to about 25% of that for 3-demethylation) was only slightly affected by the quinolones. Minor, but inconsistent, effects were found on 8-oxidation to 1,3,7-trimethyluric acid. The results indicate that the reduction of caffeine clearance by concomitant quinolone application observed in vivo is primarily due to a competitive interaction of the inhibiting quinolones with the cytochrome P-450 isoenzyme(s) mediating caffeine demethylation.

Aged↗