ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Neuromuscular blocking agents provide muscle relaxation for a great variety of surgical procedures with light planes of general anaesthesia. Besides having a significant impact in the development of anaesthesia and surgery, these agents continue to play an important role as pharmacological tools in the elucidation of the physiological and pharmacological regulation of neuromuscular transmission and the morphofunctional organisation of the neuromuscular junction. In the daily practice of anaesthesia, muscle relaxants are considered to be safe drugs with predictable, straightforward pharmacological actions. However, the use of relaxants constitutes a deliberate encroachment on respiration, one of the most important physiological mechanisms. The pharmacokinetic behaviour of this class of agents is little influenced by age or anaesthetic agents; however, hepatic or renal disease may profoundly alter their excretion pattern, resulting in prolonged duration of neuromuscular blockade. Biotransformation plays an important role in the total elimination of recently introduced compounds. Consequently, knowledge of the disposition pharmacokinetics, excretion and biotransformation of this class of drugs is indispensable for their rational choice for various surgical procedures.In this review, the known pharmacokinetics of standard compounds (introduced before 1980) are briefly summarised and new information generated by the development of vecuronium, rocuronium, pipecuronium (steroidal agents) and atracurium, mivacurium, doxacurium (benzylisoquinolinium esters) is discussed in more detail.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Fleroxacin is a new member of the class of fluoroquinolones. The drug has good activity (i.e. minimum inhibitory concentrations at less than 2 mg/L against 90% of strains) against a wide range of Gram-positive and Gram-negative bacteria. High performance liquid chromatography is used to determine concentrations of fleroxacin and its metabolites in biological fluids. Absorption of orally ingested drug is rapid as the peak plasma concentration of approximately 5 mg/L is reached in 1 to 2h after a single dose of 400mg. The systemic availability is close to 100%. Fleroxacin is poorly bound to plasma proteins (23%) and exhibits excellent tissue distribution. Renal clearance accounts for 60 to 70% of elimination. The drug is metabolised to form antimicrobially activeN-demethyl-fleroxacin and inactiveN-oxide-fleroxacin. In multiple dose studies the accumulation ratio of a once-daily dosage regimen is about 1.3, as predicted from the elimination half-life of 10 to 12h. Compared with ciprofloxacin, fleroxacin has a greater systemic availability and a longer half-life.Fleroxacin concentrations are higher in elderly patients, but further studies are needed to establish whether a dosage reduction should be recommended for this age group. In patients with renal disease dosage adjustment is recommended since a decreased renal clearance of fleroxacin leads to a significant prolongation of the elimination half-life. Fleroxacin is only poorly eliminated by peritoneal dialysis or haemodialysis.The most important drug-drug interaction is a decrease in systemic availability of fleroxacin after ingestion of aluminium- or magnesium-containing antacids. There is no evidence of a significant interaction between fleroxacin and theophylline. Only limited data are available on adverse reactions of fleroxacin. The most important adverse effects appear to be photosensitivity and a dose-dependent incidence of central nervous system reactions including sleep disorders.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Pharmacokinetic parameters of third generation cephalosporins vary widely, requiring different dosage regimens and adjustment methods for each agent. Although their antibacterial spectrum favours their usage in infections caused by aerobic Gram-negative organisms, due to their limited postantibiotic effect against these organisms, dosage regimens should ensure that free drug concentrations at the site of infection remain above the minimum inhibitory concentration for as much of the dosage interval as possible in patients with normal host defence mechanisms and for the entire dosage interval in immunocompromised patients. Altered protein binding encountered in various disease states can affect both microbiological and pharmacokinetic properties especially for drugs with high protein binding. Since the concentrations at the site of action are often different from those in serum, a higher or lower range of dosages needs to be selected depending on the target site. Decreased renal function affects the elimination of most third generation cephalosporins, whereas the presence of hepatic disease does not generally necessitate dosage adjustment. Because of the complex age-related physiological changes in paediatric and elderly patients, dosage should be adjusted on the basis of the reported pharmacokinetic data in these populations. The usual recommended dose may or may not be optimal in a given condition depending on the complex interactions between pharmacokinetic, microbiological and other host factors.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

In the present study, ribostamycin concentrations in serum were measured by microbiological assay in 20 paediatric patients aged 3 months to 11 years after intramuscular ribostamycin 10, 15 and 20 mg/kg. All pharmacokinetic parameters and statistical analyses were calculated by computer. These results showed that the absorption rate constant (ka), elimination rate constant (ke), time to peak serum concentration (tmax), elimination half-life (t½), apparent volume of distribution (Vd/F), total body clearance (CL) and area under the serum concentration-time curve (AUC) were significantly different in infants under 6 months from those in children over 3 years (p < 0.05), except for the peak serum concentration (Cmax) and lag time from administration to the first appearance of drug in the serum (tlag) [p > 0.05]. The absorption of ribostamycin in infants was more rapid than that in children, but elimination was slower (p < 0.05). The Vd/F and CL in infants were also larger than in children (p < 0.01). There were significant positive correlations between Cmax, AUC and ribostamycin dosage (p < 0.01). Pharmacokinetic parameters for infants and children were compared with those observed in adults, and it was found that ribostamycin absorption and elimination were more rapid in the paediatric patients. The Cmaxin children and infants after intramuscular ribostamycin 10 mg/kg approached that in adults after an intramuscular dose of ribostamycin 500mg. Using a 1-compartment open pharmacokinetic model, the optimum intramuscular ribostamycin administration interval was estimated as 6.01 and 7.56h for children and infants, respectively, while the value was 8.5h in adults. When the drug was administered in multiple doses of 15 mg/kg intramuscularly every 8h, no accumulation occurred in children. It is suggested that ribostamycin be administered in intramuscular doses of 10 to 15 mg/kg twice daily in infants and 3 times daily in children, respectively.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

The pharmacokinetic and pharmacodynamic properties of raclopride, a new antipsychotic, were investigated in 16 healthy men. Single 4mg doses were administered as intravenous infusion, oral solution and 2 extended release (ER) formulations.Total plasma clearance was about 100 ml/min (6.0 L/h), of which renal clearance accounted for 0.2 ml/min, indicating extensive metabolism. The volume of distribution was 1.5 L/kg; mean absolute bioavailability was 65 to 67% following the oral solution and the ER formulations.A transient increase in plasma prolactin levels followed both the intravenous infusion and the oral solution. The ER formulations resulted in a lower increase, which appeared later. However, the area under the prolactin level curve was similar after administration of all dosage forms.The frequency and severity of the most commonly reported side effects (tiredness and restlessness) were higher after the intravenous infusion than after the ER capsules. These findings indicate that such capsules may be advantageous for clinical antipsychotic treatment with raclopride.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS