摘要:

SummaryAn effort has been made to summarize clinical selection criteria for therapeutic drug monitoring for the tricyclic antidepressants (TCAs). A clear understanding of this would increase the number of patients who benefit from TCA blood-level determinations. Depression has been defined in terms of the old and new nomenclature in an attempt to clarify the ambiguities that necessarily exist in such an all-encompassing classification of disease. The biogenic amine hypothesis of depression is briefly reviewed, followed by the effect of pharmacokinetic parameters on the establishment of steady-state blood levels. The protein binding of the TCAs and the resulting effect on free versus total drug levels is discussed. Pharmaceuticals and other factors known to affect TCA blood levels are mentioned. Following a discussion of anticholinergic side effects and cardiotoxicity, therapeutic ranges for various TCAs are reviewed as to our current level of understanding. The remainder of the paper explores patient selection criteria for future clinical studies attempting to establish a drug level—effect relationship. Recent case histories are supplied throughout the text to illustrate the various subjects addressed. They also instruct the clinician and the laboratory scientist as to the potential use of TCA blood-level monitoring in the treatment of depression.

ISSN:0163-4356    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

SummaryLiquid chromatography, gas chromatography, enzyme multiplied immunotechnique, substrate-labeled fluorescence immunoassay, and radio immunoassay were applied simultaneously to the routine analysis of a number of patient serums containing phenytoin, phenobarbital, primidone, carbamazepine, ethosuximide, carbamazepine-epoxide, phenylmethylmalondiamide, andN-desmethylmethsuximide. Analytical performance, practicability, and economy of the various methods were compared.

ISSN:0163-4356    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

SummaryThe pharmacokinetics of a single dose of intravenous ampicillin were studied in nine patients during their third trimester of pregnancy. Each volunteer was given either 500 mg (5.7–8.8 mg/kg) or 1 g (15.4–21.4 mg/kg) of sodium ampicillin by rapid infusion. Postinfusion plasma concentration—time curves followed biexponential decay in all subjects. Calculated parameters included a mean plasma distribution volume of 177.1 ± 97.5 ml/kg, tissue or peripheral distribution volume of 246.2 ± 143.9 ml/kg, elimination half-life of 1.60 ± 0.51 h, and total body clearance of 4.59 ± 1.48 ml/min/kg. Dose-dependent disposition was not observed. Gestation-specific drug therapy research during pregnancy is discussed.

ISSN:0163-4356    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

SummaryThe pharmacokinetics of rifampicin (RMP) and its principal active metabolite desacetylrifampicin (DA-RMP) were studied in six subjects, ranging in age from 78 to 95 years, after single oral doses of 10 mg/kg RMP. The maximal plasma concentrations (Cmax) and the elimination half-lives (t1/2β) of RMP are 8.83 ± 1.72 mg L-1and 4.09 ± 2.59 h, respectively. They are comparable to those reported in young adults. The same applies to the Cmaxvalue (1.93 ± 0.53 mg L-1) and t1/2βvalue (4.65 ± 2.61 h) of DA-RMP. However, the renal clearance of RMP (0.0075 ± 0.0036 L h-1) and the amounts of RMP (20.7 ± 9.9 mg) and DA-RMP (13.3 ± 5.6 mg) excreted in the urine during a 24-h period are lower than those reported in young adults. The renal excretion of RMP and DA-RMP, therefore, is reduced in the elderly. But since the drug is also excreted through the liver to such an extent that serum levels are the same as in young adults, for therapeutic purposes the metabolism of RMP may be globally considered as unaltered in elderly patients.

ISSN:0163-4356    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

SummaryFour rates of rifampicin infusion ranging from 3.3 to 15 mg/min in 12 tuberculous patients were studied. Blood samples (n = 10) were drawn during infusion and 8 h later. Urine samples were collected in six fractions during a 24-h period. Rifampicin and desacetylrifampicin were measured by high-pressure liquid chromatography. Results show that the maximum plasma concentrations increase linearly for each dose with the rate of infusion, and that the amounts excreted in the urines are highly dependent on the administered dose. Simulation of plasma concentrations after different dosage regimens shows that a double rate of infusion—20 mg min-1during 1 h and then 200 mg h-1—allows plasma concentrations to be quickly reached and maintained at a 20 mg L-1level, far higher than the minimum inhibitory concentrations of most germs.

ISSN:0163-4356    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

SummaryThe effects of age and associated therapy on plasma primidone (PRM) and derived phenobarbital (PB) concentrations, and on plasma concentrations-to-PRM dose ratios (L/D ratio) were evaluated retrospectively from 408 consecutive PRM and derived PB determinations in 238 chronically treated epileptic patients (153 children and adolescents between 5 months and 15 years of age and 85 adults between 16 and 55 years of age). The correlation between PRM administered and both plasma PRM and derived PB levels was significant; the correlation between PRM and PB plasma levels was also significant, but the scatter of values for the linear regressions was such that the relationship had no predictive value. Significant differences in mean plasma PRM and PB L/D ratios were found between patients aged 0–3 years, 4–9 years, 10–15 years, and adults (16–55 years), with higher values in the older groups. The PB/PRM concentration ratios were significantly lower in children than in adolescents and adults. Concomitant treatment with carbamazepine affected PRM disposition and led to increased L/D ratios for PB and decreased L/D ratios for PRM, whereas phenytoin increased the L/D ratios for PB without any significant change in the L/D ratios for PRM. The variability in the results indicates the need for routine monitoring of PRM and derived PB plasma levels, particularly in pediatric populations, in order to tailor the dose to each patient.

ISSN:0163-4356    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

SummaryAn ultrafiltration technique, using Ultrafree Anticonvulsant Drug Filters, was compared to equilibrium dialysis for the determination of disopyramide plasma protein binding. Mean total recovery of drug was 92.4% for ultrafiltration compared with 98.4% for equilibrium dialysis. At initial plasma concentrations spanning the therapeutic range (2–8 μg/ml), the percentage binding of disopyramide was concentration dependent for both methods (78–38%). Initial experiments with ultrafiltration (1 ml of plasma) indicated a small (0.14%) but variable loss of total plasma protein in the ultrafiltrate (0.1-ml volume). In ultrafiltration, percentage binding of disopyramide was similar at 22 and 37°C, whereas in equilibrium dialysis, binding was significantly (p < 0.001) greater (1.4–2.7%) at 22 than at 37°C. Percentage binding for plasma (1-ml volume), assessed at ultrafiltrate volumes of approximately 0.1 and 0.25 ml, was found to be significantly (p < 0.05) different, but in practical terms the mean difference was

ISSN:0163-4356    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

SummaryHigh-performance liquid chromatographic assays for propranolol and its major metabolites in plasma and breast milk are described. The breast milk/whole plasma ratios of propranolol in three lactating women were in the range of 0.33 to 1.65. The half-life of elimination of propranolol from breast milk was 6.5 ± 3.4 h (mean ± SD), which was significantly longer (t = 1.844, df = 4, p < 0.01) than the half-life of elimination of propranolol from plasma, which was 2.6 ± 1.2 h (mean ± SD). The half-life of elimination of the propranolol metabolite naphthoxylactic acid from breast milk was 4.2 ± 0.9 h (mean ± SD), which was not significantly different (t = 0.042, df = 4, p > 0.05) from the mean half-life of elimination from plasma, which was 4.2 ± 1.2 h (mean ± SD). The penetration of propranolol glucuronide into breast milk was slower and to a lesser extent than that of propranolol and naphthoxylactic acid. The maximum dose, calculated from the results presented in this paper, ingested as either propranolol or as propranolol glucuronide in breast milk by the neonate would be

ISSN:0163-4356    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

SummaryWe have studied 19 male patients whose theophylline therapy was individualized by a clinical pharmacokinetics service and 34 male patients with empirically derived dosages. All patients were admitted to the medical intensive care unit. Patients in the pharmacokinetics group had fewer adverse reactions (15.7 vs. 50%), shorter intensive care unit stay (6.6 ± 5.5 vs. 12.4 ± 16.3 days), shorter hospital stay (15.4 ± 10 vs. 22.3 ± 14.1 days), and a shorter period of time to be placed on oral therapy (5.3 ± 2.1 vs. 8.6 ± 7.2 days) than the group with empirically derived regimens. The pharmacokinetic method used to individualize theophylline therapy offered an accurate and efficient method of achieving therapeutic concentrations. We conclude that the use of clinical pharmacokinetics to individualize theophylline therapy offers substantial benefits over empirical assessments.

ISSN:0163-4356    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

SummaryThe predictive ability of the “condition correction factor” method of estimating total body theophylline clearance as proposed by Powell et al. was evaluated in 22 acutely ill hospitalized patients. Actual theophylline clearance was calculated while the patient was on a constant infusion of aminophylline with serum theophylline concentrations obtained at steady-state conditions. Independently, theophylline clearance was estimated for each patient using condition correction factors. The relationship between actual and estimated total body theophylline clearance was evaluated using multiple regression analysis and correlation testing. The data failed to demonstrate any significant positive correlation between actual and estimated theophylline clearance data. Because of this poor correlation, the use of one of the clearance estimation methods incorporating two serum theophylline concentrations obtained early in therapy is preferable, although less convenient. All estimates of clearance must be considered only as guides for individualization of therapy. Serum concentration monitoring and clinical response of the patient must be considered prior to adjustment of dosage.

ISSN:0163-4356    

出版商:OVID    

年代:1983

数据来源: OVID