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Biomedical subjects

S Harder

Publications and source records attributed to S Harder.

126 records · Page 7Linked to original sources
PubMed1988

4-quinolones inhibit biotransformation of caffeine.

The pharmacokinetics of caffeine, including formation of its major metabolite paraxanthine in plasma, has been investigated in 12 healthy males (age 20-40 years) alone and during co-administration of the 4-quinolones ofloxacin, norfloxacin, pipemidic acid, ciprofloxacin, and enoxacin; ciprofloxacin and enoxacin were given in 3 different dose levels. The naphthyridine derivative enoxacin and the pyrido-pyrimidine derivative pipemidic acid had caused marked inhibition of caffeine and paraxanthine metabolism, whereas the genuine quinolone derivatives norfloxacin and ciprofloxacin had little effect, and the pyrido-benzoxacine derivative ofloxacin had no detectable effect. The different molecular and spatial structures of the compounds appear to be responsible for the differences in inhibitory potency.

Adult↗
PubMed1988

Experimental rhinovirus infection in human volunteers exposed to ozone.

We studied 24 young adult male volunteers experimentally inoculated with type 39 rhinovirus to determine whether the course of viral infection was modified by exposure to moderate levels of ozone (0.3 ppm for 6 h per day) over the 5 days after virus inoculation. No differences in rhinovirus titers in nasal secretions, recruitment of neutrophils into nasal secretions, levels of interferon in nasal lavage fluid, in vitro lymphocyte proliferative responses to rhinovirus antigen, or levels of convalescent serum neutralizing antibody to type 39 rhinovirus were demonstrated in relation to ozone exposure. The level and pattern of ozone exposure used in this experiment had no demonstrable adverse effects on the immune responses necessary to limit and terminate rhinovirus infection of the upper respiratory tract.

Adult↗
PubMed1987

Decrease of caffeine elimination in man during co-administration of 4-quinolones.

The single dose pharmacokinetics of caffeine (220-230 mg per dose) were investigated in 12 healthy male volunteers before and during treatment with ofloxacin (200 mg bd), ciprofloxacin (250 mg bd) and enoxacin (400 mg bd) with a cross-over study design. None of the parameters: mean elimination half-life (T1/2el), Cmax, total body clearance (Cltot) and the volume of distribution (aVd) of caffeine were noticeably altered by administration of ofloxacin. Striking changes were observed, however, after administration of enoxacin: the T1/2el was prolonged by as much as 260%, the Cmax increased by 41%; the aVd was reduced by 20% and Cltot by 78% (mean values). Treatment with ciprofloxacin led to a prolongation of T1/2el by 15%, to a decrease of aVd by 25% and to a 33% decrease of Cltot. The results of this intra-individual comparison of caffeine pharmacokinetic data demonstrate that treatment with ciprofloxacin and enoxacin may have a significant inhibitory effect on caffeine elimination.

Adult↗
PubMed1987

Interaction between quinolones and caffeine.

The effects of multiple doses of ofloxacin 200 mg, ciprofloxacin 250 mg or enoxacin 400 mg (all twice daily) on the pharmacokinetic properties of single doses of caffeine (220 to 230 mg) were investigated in 12 healthy volunteers. Intraindividual comparisons showed that ciprofloxacin and enoxacin significantly inhibited the elimination of caffeine. Ofloxacin, however, did not affect any of the measured pharmacokinetic properties of caffeine. Thus, caffeine should be avoided in patients with liver disorders, cardiac arrhythmias, latent epilepsy or in intensive care while undergoing treatment with enoxacin or ciprofloxacin.

Adult↗
PubMed1986

Measurement of theophylline absorption from different regions of the gastro-intestinal tract using a remote controlled drug delivery device.

The absorption of a theophylline solution containing 80-120 mg doses delivered to different sites in the gastro-intestinal tract has been determined in 3 male volunteers using a remote controlled drug release system (HF-capsule). There was no difference between the stomach, ileum and the colon in the amount of theophylline absorbed (AUC). The T 1/2abs of theophylline absorbed via the colon was prolonged when compared with that entering via the upper gastro-intestinal tract. The results provide a rational basis for the further development of theophylline formulations and are indispensable for planned development and to account for variation in the bioavailability of retarded release drug preparations.

Absorption↗
PubMedDate not supplied

CSF pharmacokinetics of ceftazidime in neurosurgical patients with an external ventriculostomy.

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

[Undesirable drug reactions in simultaneous administration of high-dosage phenobarbital and beta-lactam antibiotics].

The present paper reports on a striking increase in undesirable drug induced reactions during simultaneous administration of high-dosage phenobarbital and beta-lactam antibiotics to children in intensive care. In a 30-month study period, reactions which had to be classified as drug-induced were seen in 24 out of a total of 49 children (mainly exanthematous skin reactions, in some cases severe). The complications were mainly observed in patients receiving a combination of cefotaxime and phenobarbital. Etiologically, a toxic reaction to the combination of hepatically metabolized beta-lactam antibiotics with an enzyme-inducing drug must be considered in addition to the allergenic potential of the individual components.

Anti-Bacterial Agents↗
PubMedDate not supplied

In vitro responsiveness of lymphocytes to phytohemmagglutinin.

Peripheral blood lymphocytes from 20 human subjects exposed to 784 microgram/m3 ozone for 4 hours, and from 11 subjects exposed to clean air for the same length of time were studied for in vitro responsiveness to phytohemagglutinin (PHA). Thymus-derived (T) lymphocyte response to PHA (normal response is proliferation of lymphocytes) was significantly suppressed (P less than .01) in samples obtained immediately after subjects' exposure to ozone. Recovery of response occurred 2 weeks postexposure. Responses were unchanged in subjects exposed to clean air. Existing studies suggest that ozone exposure may generate free radicals or other reactive molecules or both, that could be responsible for immediate changes in metabolic events leading to blockage or inhibition of deoxyribonucleic acid (DNA) synthesis in T lymphocytes as shown in this study. It is possible that some prerequisite to active cell metabolism such as ribonucleic acid (RNA) may be impaired by ozone exposure. The significance of the suppression of T-cell response noted in this study is that: (1) if continuous exposures to ozone are shown to induce an immunosuppressed state for a significant time period, an important factor in carcinogenesis might be elucidated; (2) immunosuppression may cause a progression of an already present tumor; (3) immunosuppression may enable endogenous latent infections such as tuberculosis to reactivate; and (4) immunosuppression may explain in part the relationship between chronic oxidant air pollution and influenza-like illnesses in population.

Adult↗
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↗
PubMedDate not supplied

Pharmacodynamics of levodopa coadministered with apomorphine in parkinsonian patients with end-of-dose motor fluctuations.

The modification of the pharmacodynamic response to a single oral dose of levodopa/benserazide by the coadministration of the dopamine agonist apomorphine was investigated in parkinsonian patients with end-of-dose motor fluctuations. The relation between levodopa plasma concentrations and motor response was examined in a double-blind, randomized, crossover design in 10 patients with idiopathic Parkinson's disease with end-of-dose motor fluctuations. Oral single-dose challenges with 100 mg of levodopa/25 mg of benserazide were carried out twice in each patient, under coadministration with apomorphine (1 mg/h) or 0.9% saline (placebo) subcutaneously. The sum scores (sigma score) of the Columbia University Rating Scale (CURS) were used as effect parameters for pharmacodynamic assessment. A sigmoidal Emax model was fitted to the data using a semiparametric pharmacokinetic-pharmacodynamic approach. Levodopa pharmacokinetics were not significantly modified by the coadministration of apomorphine. The area under the curve was 1599 +/- 615 ng.ml-1 h. (levodopa + saline) and 1821 +/- 625 ng.ml-1.h (levodopa + apomorphine). Cmax was 1094 +/- 476 ng.ml-1 (levodopa + saline) and 1129 +/- 435 ng.ml-1 (levodopa + apomorphine). Under both experimental regimens, the maximum clinical response to levodopa (Emax) yielded a decrease in the CURS sigma rating of about 20 score points. Estimates of the EC50 of levodopa decreased significantly from 430 +/- 163 ng.ml-1 (levodopa + saline) to 315 +/- 123 ng+ml-1 (levodopa + apomorphine) (95% confidence interval [CI] 0.51 -0.98, point estimator 0.75). The mean duration of the motor response rose from 1.9 +/- 0.5 h (levodopa + saline) to 3.0 +/- 0.9 h (levodopa + apomorphine (95% CI 1.23 to 2.06, point estimator 1.60). Thus, a reduction of the threshold levels for levodopa (EC50) was accompanied by approximately 50% gain in on-phase duration, but not in an increased magnitude of the motor response (Emax).

Adult↗