ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Epilepsy is a chronic disease that requires long term therapy, and most of the established antiepileptic drugs (the exception is phenobarbital) must be administered several times daily. This results in compliance problems and fluctuations in plasma concentrations which may lead to subtherapeutic and potentially toxic levels. Development of sustained release formulations of the existing antiepileptic agents may improve antiepileptic therapy. At present, only the following 4 major drugs are used for the treatment of epilepsy: phenobarbital, phenytoin, carbamazepine and valproic acid. Of these, only the latter 2 are suitable candidates for sustained release formulations. This review, therefore, focuses on the evaluation and clinical implications of sustained release formulations of valproic acid and carbamazepine.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Amlodipine is a dihydropyridine calcium antagonist drug with distinctive pharmacokinetic characteristics which appear to be attributable to a high degree of ionisation. Following oral administration, bioavailability is 60 to 65% and plasma concentrations rise gradually to peak 6 to 8h after administration. Amlodipine is extensively metabolised in the liver (but there is no significant presystemic or first-pass metabolism) and is slowly cleared with a terminal elimination half-life of 40 to 50h. Volume of distribution is large (21 L/kg) and there is a high degree of protein binding (98%). There is some evidence that age, severe hepatic impairment and severe renal impairment influence the pharmacokinetic profile leading to higher plasma concentrations and longer half-lives. There is no evidence of pharmacokinetic drug interactions. Amlodipine shows linear dose-related pharmacokinetic characteristics and, at steady-state, there are relatively small fluctuations in plasma concentrations across a dosage interval.Thus, although structurally related to other dihydropyridine derivatives, amlodipine displays significantly different pharmacokinetic characteristics and is suitable for administration in a single daily dose.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Ofloxacin is a new fluoroquinolone with a spectrum of activity similar to other fluoroquinolones with activity which includesChlamydia trachomatis, Mycobacteriumspp.,Mycoplasmaspp. andLegionella pneumophila.Through its additional mechanisms of action, ofloxacin may be less susceptible to the development of resistance fromStaphylococcus aureuscommonly seen with currently available fluoroquinolones. The impact of these findings cannot be evaluated without further clinical experience. The pharmacokinetics of ofloxacin are characterised by almost complete bioavailability (95 to 100%), peak serum concentrations in the range of 2 to 3 mg/L after a 400mg oral dose and an average half-life of 5 to 8h. In comparison with other available quinolones, elimination is more highly dependent on renal clearance, which may lead to more frequent dosage adjustments in patients with impaired renal function. Ofloxacin appears less likely to affect the pharmacokinetics of drugs (e.g. theophylline) which commonly interact with fluoroquinolones such as ciprofloxacin and enoxacin. The properties of ofloxacin make it a therapeutic alternative to currently available fluoroquinolones.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Rifampicin, an antituberculosis drug, is usually administered for 4 to 12 months with other antituberculosis drugs or medications from other classes. A potential for drug interactions often exists because rifampicin is a potent inducer of hepatic drug metabolism, as evidenced by a proliferation of smooth endoplasmic reticulum and an increase in the cytochrome P450 content in the liver. The induction is a highly selective process and not every drug metabolised via oxidation is affected.Case reports and studies have demonstrated enhanced metabolism of several drugs; most of these interactions are clinically important. At the start of rifampicin treatment, and again at the end, clinicians must check the dosages of any accompanying medications with which rifampicin may potentially interact. Monitoring of clinical response and blood drug concentrations is essential to adjust the drug dosage during rifampicin therapy.Rifampicin also interacts with cholephils such as bilirubin and bromosulphthalein. Its pharmacokinetics are reported to be altered by ethambutol,p-aminosalicylic acid (through its excipient component), ketoconazole, cyclosporin, clofazimine, probenecid and phenobarbital through one or other of the following mechanisms - impaired absorption of rifampicin, competition between the drug and rifampicin for hepatic uptake and altered hepatic metabolism of rifampicin. Most interactions affecting rifampicin have been relatively minor or are not expected to alter its therapeutic efficacy.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

It was the purpose of this study to evaluate the effect of quinidine administration on the population estimates of the volume of distribution (Vdpop) and clearance (CLpop) of digoxin. The data collected on 94 patients included 230 measured serum digoxin concentrations, height, age, sex, weight (wt), serum creatinine, history of digoxin and quinidine administration and the presence or absence of congestive heart failure (CHF). Using the NONMEM software program, estimates were obtained for CLpopand Vdpop. Variables tested for inclusion in the CLpopmodel were creatinine clearance (CLCR), CHF, wt, ideal bodyweight, quinidine (QUIN) [both as a discrete variable and in a dose-dependent manner], and body surface area. Variables tested for inclusion in the Vdpopmodel were CLCR, wt, ideal bodyweight, body surface area and quinidine. During model building a p-value of 0.05 was chosen for variable inclusion. The final model was as follows:CLpop(L/h) = (3.1 + 0.0516 × CLCR) × QUINVdpop(L) = (4.03 + 0.0832 × CLCR) × wtF = 0.82where F is bioavailability. In the above, QUIN is 0.567 if quinidine is being concurrently administered and 1.0 if it is not. The coefficient of variation (CV) of CLpopwas 44% while that of Vdpopwas 48%. The residual intrasubject CV was 26%. These results compare favourably with previously derived methods of estimating digoxin CLpopand Vdpopbut may improve on those methods due to the inclusion of quinidine in the model. These better estimates should result in improved initial dosage of digoxin.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

The influence of age on the systemic absorption and disposition of bupivacaine following epidural administration in 20 male patients (22 to 81 years) was examined using a stable isotope method to determine whether pharmacokinetics play a role in age-related pharmacodynamic changes seen with the drug. After epidural bupivacaine administration a deuterium-labelled analogue was administered intravenously. Bi- and triexponential functions were fitted to plasma concentration-time data of deuterium-labelled bupivacaine. The systemic absorption was described by 2 parallel first-order absorption processes. The upper level of analgesia and the duration of analgesia at dermatome T-12 increased with age (r = 0.68, p < 0.001; r = 0.56, p < 0.01, respectively). The time to maximal caudad spread of analgesia and the time to onset of motor block decreased with age (r = −0.76, p < 0.0001; r = −0.72, p < 0.001, respectively). Age did not influence systemic absorption or disposition of bupivacaine. We conclude that the changes in the clinical profile of bupivacaine with age are not due to altered pharmacokinetics, but may be related to changes in the pharmacodynamics of the drug.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS