ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

Mefloquine, a quinolinemethanol antimalarial, is effective single dose therapy for all species of malaria infecting humans, including multi-drug-resistantPlasmodium falciparum.It is used both in prophylaxis and treatment. Mefloquine is available either as the hydrochloride salt alone, or in a combined preparation with sulfadoxine and pyrimethamine. There is no parenteral formulation. Several assay methodologies have been developed, but high performance liquid chromatography has been the most used in recent pharmacokinetic studies. These have shown in healthy volunteers that mefloquine is absorbed with a half-life of 1 to 4 hours and a time to peak concentration of 7 to 24 hours (median 16.7 hours). Mean peak blood concentrations have ranged between 50 and 110 (median 83) ng/ml/mg/kg. Estimates of total apparent volume of distribution (Vd/f) have ranged from 13.3 to 40.9 (median 19.2) L/kg, systemic clearance (CL/f) from 0.022 to 0.073 L/h/kg (median 0.026 L/h/kg), and terminal elimination half-life from 13.8 to 40.9 days (median 20 days). Systemic clearance appears to be increased in late pregnancy. In uncomplicated falciparum malaria, peak blood concentrations are 2 to 3 times higher than those in healthy subjects ranging from 112 to 209 (median 144) ng/ml/mg/kg because of contraction in the total apparent volume of distribution. Systemic clearance is usually reduced but elimination rates are increased (possibly because of reduced enterohepatic recycling). Mefloquine absorption appears to be reduced in severe falciparum malaria; plasma protein binding exceeds 98% in both healthy subjects and patients. No important drug interactions have been identified as yet, but the potential for serious interactions with quinine has not been adequately investigated. More studies are needed on the disposition of mefloquine in children.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

Neonatal patients are surviving longer due to the rapid advances in medical knowledge and technology. Our understanding of the developmental physiology of both preterm and full term neonates has also increased. It is now apparent that differences in body composition and organ function significantly affect the pharmacokinetics of antibacterial drugs in neonates, and dosage modifications are required to optimise antimicrobial therapy.The penicillins and cephalosporins are frequently used in neonates. Although ampicillin has replaced benzylpenicillin (penicillin G) for empirical treatment of neonatal sepsis, many of the other penicillins may be used in neonates for the management of various infections. Increased volume of distribution (Vd) and decreased total body clearance (CL) affect the disposition of penicillins and cephalosporins. Decreased renal clearance (CLR) due to decreased glomerular filtration and tubular secretion is responsible for the decreased CL for most of the&bgr;-lactams.Aminoglycoside Vd is affected by the increased total body water content and extracellular fluid volume of neonates. The increased Vd, in part, accounts for the extended elimination half-life (t½) observed in neonates. Aminoglycoside CL is dependent on renal glomerular filtration which is markedly decreased in neonates, especially those preterm. These drugs appear to be less nephrotoxic and ototoxic in neonates than in older patients, and the role of serum concentration monitoring should be limited to specific neonatal patients.Other antibiotics such as vancomycin, teicoplanin, chloramphenicol, rifampicin, erythromycin, clindamycin, metronidazole and cotrimoxazole (trimethoprim plus sulfamethoxazole) may be used in certain clinical situations. The emergence of staphylococcal resistance to penicillins has increased the need for vancomycin. With the exceptions of vancomycin and chloramphenicol, the efficacy and safety of these other agents in neonates have not been established. The need for serum vancomycin concentration monitoring may be limited, as with aminoglycosides, while safety concerns warrant the routine monitoring of serum chloramphenicol concentrations in neonates.Dosing guidelines are provided, based on the pharmacokinetics of the drugs and previously published recommendations. These dosing guidelines are intended for initial therapy, and close therapeutic monitoring is recommended for maintenance dose requirements to optimise patient outcome.There has been an enormous increase in our knowledge of neonatal physiology and drug disposition. Fortunately, many of the antibacterial drugs used in neonates (e.g. penicillins and cephalosporins) are relatively safe. It will be important to evaluate all newly developed antibiotics in neonates to assure their maximum efficacy and safety.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

This article reviews the reported pharmacokinetic interactions between cyclosporin and other drugs. Both rifampicin and the majority of anticonvulsants can decrease cyclosporin concentrations to levels that are at or below the limit of detection for most assays. There have been no reports of any interaction between valproic acid and cyclosporin. Other drugs that have been reported to decrease cyclosporin concentration include sulfadimidine and trimethoprim, nafcillin and octreotide.Erythromycin, ketoconazole and some calcium channel blockers have been clearly shown to increase the concentration of cyclosporin. Other less well documented interactions have been reported with other macrolide antibiotics, other azole antifungal drugs, high dose methylprednisolone, metoclopramide, fluoroquinolones, imipenem/cilastatin, oral contraceptives/danazol, sulindac, methyltestosterone, colchicine, acetazolamide, alcohol and cimetidine. Although the most commonly reported mechanism is inhibition of cyclosporin metabolism, there is increasing evidence that erythromycin, metoclopramide and probably other drugs increase the bioavailability of oral cyclosporin. Two calcium channel blockers which have not been reported to interact with cyclosporin are nifedipine and nitrendipine.With increasing use of cyclosporin, the number of drugs reported to interact will rise. Prudent clinicians should monitor the concentration of this agent more frequently when another drug is added or discontinued and cyclosporin dosage should be adjusted when appropriate. Sustained changes in cyclosporin concentration can result in graft rejection (or graft-versus-host disease) or renal toxicity. Further studies are needed to determine the mechanism of most of these interactions.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

The pharmacokinetics of gentamicin were studied after total hip joint arthroplasties in 2 groups of 10 patients. The prosthesis was performed in the first group with ‘Palacos R plus gentamicin’ (normal viscosity), manufactured by Schering, and in the second group with ‘Cerafix genta R’ (low viscosity) manufactured by Ceraver-Osteal. Both cements included similar concentrations of gentamicin. Urine was collected at 12-hour intervals for 15 days after operation, and drainage fluids for 48, 72 or 108 hours. Blood samples were taken 3 and/or 5 hours after prosthesis implantation.In both cases, high concentrations of gentamicin were found in drainage fluids and urine during the early postoperative period. Mean gentamicin excretion curves were calculated by a computer-aided design program (SIAM) for the 2 cements. The release of gentamicin was biphasic in both cases, although the slow elimination phase appeared to be longer for ‘Cerafix’. In the first postoperative period, the drug had a better bioavailability during the rapid elimination phase in the case of ‘Palacos’. The calculated peak blood concentration was in the same range for both compounds.The conclusion is drawn that, in patients undergoing total hip joint arthroplasties, gentamicin concentrations reach local levels higher than the minimum inhibitory concentrations of most of the likely sensitive pathogens. However, in both cases, as blood concentrations appear to be low, patients will not be protected against systemic infections. Both cements have similar antibacterial properties but the mechanical properties of ‘Cerafix’ are the better of the two.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS