ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

Compared with nalidixic acid, ciprofloxacin is representative of a newer, more potent class of quinolones, termed the fluoroquinolones. It is available in both oral and parenteral dosage forms.The primary target of quinolone activity appears to be the bacterial DNA gyrase enzyme, which is a member of the class of type II topoisomerases. Bacteria do not acquire resistance to fluoroquinolones through mechanisms that are plasmid or R-factor mediated and, additionally, the quinolones do not appear to be vulnerable to degradation by bacterial inactivating mechanisms. Rather, bacterial resistance to ciprofloxacin occurs either through chromosomal mutation in the target enzyme DNA gyrase or through mutations that alter drug permeability into the bacterial cell. Ciprofloxacin and the fluoroquinolones in general are no more likely to select resistant mutants than are aminoglycosides or &bgr;-lactam antibiotics.Ciprofloxacin displaysin vitroactivity against most Gram-negative and many Grampositive pathogenic bacteria, many of which are resistant to a wide range of antibiotics. This finding is of considerable potential clinical significance.High pressure liquid chromatography (HPLC) and microbiological agar diffusion assays have been routinely used to quantify ciprofloxacin concentrations in biological fluids. Both methods are reproducible and accurate for serum but HPLC is recommended for other specimens because of the presence of microbiologically active metabolites.Absorption after oral administration is rapid and can be satisfactorily described as a zero-order process; peak serum ciprofloxacin concentrations (Cmax) are reached in approximately 1 to 2 hours. Concomitant administration of food does not cause clinically significant impairment of absorption and may be helpful in minimising gastric distress caused by the drug. A linear relationship between serum ciprofloxacin concentrations and the dose administered either orally or intravenously has been reported. The absolute bioavailability of ciprofloxacin is approximately 70%. The volume of distribution is large with a steady-state range after oral or intravenous dosing of 1.74 to 5.0 L/kg reflecting penetration of the drug into most tissues.Nonrenal clearance accounts for approximately 33% of the elimination of ciprofloxacin; to date, 4 metabolites have been identified. A first-pass effect has been reported but is thought to be clinically unimportant. Faecal recovery of ciprofloxacin accounts for approximately 15% of an intravenous dose. Nonrenal elimination includes metabolic degradation, biliary excretion and transluminal secretion across the enteric mucosa.Glomerular filtration and tubular secretion account for approximately 66% of the total serum clearance. The terminal disposition half-life (t½) is about 3 to 4 hours. Pharmacokinetic studies after multiple intravenous doses of ciprofloxacin have not reported significant differences in terminal disposition half-lives or systemic clearances between the first and the last dose.The pharmacokinetics of ciprofloxacin in the elderly are significantly different from those observed in the young: the elderly have a reduced renal clearance, a significantly greater area under the concentration-time curve (AUC), a larger Cmax, and a prolonged t½. Several investigators have suggested that dosage intervals shorter than 12 hours be avoided in the elderly. The pharmacokinetics of ciprofloxacin in patients with cystic fibrosis do not differ significantly from those of healthy control populations and, as a result, dosing regimen alterations are not required in patients with cystic fibrosis.In patients with varying degrees of renal dysfunction, the pharmacokinetics of ciprofloxacin are significantly altered; the t½in end-stage renal disease is approximately twice that of healthy controls (≈ 8h). The observed AUC and Cmaxmay also be elevated in these patients. A wide variability in the t½of ciprofloxacin has been observed among patients with severe renal failure, resulting in the recommendation that changes be made in the daily dose rather than the dosing interval in order to achieve drug concentrations comparable with those observed in normal renal function. The clinical impact of chronic ambulatory peritoneal dialysis or haemodialysis over a 4-hour period on the pharmacokinetics of ciprofloxacin is not significant, and therefore dosage supplementation after or during these procedures is not necessary. Liver dysfunction also appears to exert little effect on ciprofloxacin pharmacokinetics and dosage adjustments are not recommended.The concomitant oral administration of magnesium-, aluminium-, or calcium-containing antacids, sucralfate, iron preparations and multivitamins containing zinc significantly reduces the absorption of ciprofloxacin. Ciprofloxacin reduces the metabolism of theophylline by approximately 15 to 30%; caution is therefore advised when using any fluoroquinolone in combination with xanthine compounds. Case reports have documented increases in prothrombin times among patients receiving warfarin and ciprofloxacin concomitantly.Adverse reactions associated with ciprofloxacin administration are generally mild to moderate and usually do not result in termination of therapy; the worldwide incidence is in the range of 4 to 8%, which is similar to that reported for other fluoroquinolones. The most commonly reported adverse reactions involve either the gastrointestinal tract (nausea, vomiting and diarrhoea), metabolic or nutritional disorders, or the CNS.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

Respiratory disorders induce several pathophysiological changes involving gas exchange and acid-base balance, regional haemodynamics, and alterations of the alveolocapillary membrane. The consequences for the absorption, distribution and elimination of drugs are evaluated.Drug absorption after inhalation is not significantly impaired in patients. With drugs administered by this route, an average of 10% of the dose reaches the lungs. It is not completely clear whether changes in pulmonary endothelium in respiratory failure enhance lung absorption. The effects of changes in blood pH on plasma protein binding and volume of distribution are discussed, but relevant data are not available to explain the distribution changes observed in acutely ill patients. Lung diffusion of some antimicrobial agents is enhanced in patients with pulmonary infections. Decreased cardiac output and hepatic blood flow in patients under mechanical ventilation cause an increase in the plasma concentration of drugs with a high hepatic extraction ratio, such as lidocaine (lignocaine). On a theoretical basis, hypoxia should lead to decreased biotransformation of drugs with a low hepatic extraction ratio, butin vivodata with phenazone (antipyrine) or theophylline are conflicting. The effects of disease on the lung clearance of drugs are discussed but clinically relevant data are lacking.The pharmacokinetics of drugs in patients with asthma or chronic obstructive pulmonary disease are reviewed. Stable asthma and chronic obstructive pulmonary disease do not appear to affect the disposition of theophylline or&bgr;2-agonists such as salbutamol (albuterol) or terbutaline. Important variations in theophylline pharmacokinetics have been reported in critically ill patients, the causes of which are more likely to be linked to the poor condition of the patients than to a direct effect of hypoxia or hypercapnia. Little is known regarding the pharmacokinetics of cromoglycate, ipratropium, corticoids or antimicrobial agents in pulmonary disease. In patients under mechanical ventilation, the half-life of midazolam, a new benzodiazepine used as a sedative, has been found to be lengthened but the underlying mechanism is not well understood. Pulmonary absorption of pentamidine was found to be increased in patients under mechanical ventilation. Pharmacokinetic impairment does occur in patients with severe pulmonary disease but more work is needed to understand the exact mechanisms and to propose proper dosage regimens.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

Pancuronium is frequently used in coronary artery surgery, but its pharmacokinetics in these patients are still unknown. It is possible that dopamine, administered to prevent renal impairment induced by the surgery, might promote the elimination of pancuronium. Therefore, the pharmacokinetics of a bolus dose of pancuronium were studied in 2 groups of coronary artery surgery patients, with and without dopamine 2μg/kg/min, administered during and after cardiopulmonary bypass. Dopamine in the administered dose did not influence the systemic haemodynamics. The pharmacokinetic variables in both groups did not differ from those found in an earlier study in healthy normothermic patients. Total renal clearance was not influenced by dopamine. due to post-bypass rebound hyperperfusion in the control group. Pancuronium was shown to be subject to considerable tubular reabsorption, and its elimination was found to be increased during hypothermia. Dopamine increases pancuronium elimination by an increase in glomerular filtration rate. The dopamine-induced decrease in tubular solute reabsorption did not enhance the elimination of pancuronium.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

Cyclosporin is an immunosuppressive agent commonly used in transplant patients. It is actively metabolised by the cytochrome P450 system and interactions with drugs metabolised by the same system are predictable. This is particularly relevant since cyclosporin has a low therapeutic index and its renal toxicity is concentration-related.Roxithromycin, a new, well-tolerated macrolide with a weak interactive profile, uses the same isoenzyme of the P450 system as cyclosporin. To evaluate its interaction potential in clinical practice, 8 heart transplant recipients treated with cyclosporin for at least 1 month received roxithromycin for 11 days (150mg twice daily). Bi-weekly controls of plasma cyclosporin concentrations and creatinine levels were carried out before, during and after roxithromycin treatment. A slight nonsignificant rise in cyclosporin concentrations was observed, but creatinine levels remained stable during roxithromycin treatment. Values of cyclosporin concentrations diminished after withdrawal of roxithromycin. Cyclosporin dosage adjustment was not necessary. There was a minor pharmacokinetic interaction, which can be considered safe for the usual therapeutic dosage of roxithromycin used.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS