摘要:

Hypertension is a disease more common to advanced societies, possibly due to diet and life style. It is a disease that can be readily controlled, and active efforts to decrease blood pressure correlate with decreased incidence of cardiovascular disease. Important in the armamentarium of the physician dealing with hypertension are a variety of drugs. The common drugs include diuretics (thiazides, loop of Henle diuretics, potassium-sparing diuretics), β-blockers, α-agonists, neuron-blocking drugs, and vasodilators. The role of monitoring the blood concentration of each of these drugs in the interest of enhancing clinical usefulness is reviewed in light of the pharmacology of each drug group. We conclude that clonidine, guanethidine, hydralazine, and prazosin have properties that lend themselves to monitoring. Propranolol, metoprolol, nadolol, and α-methyldopa are drugs that have pharmacological properties that complicate monitoring. The drugs reserpine and minoxidil have properties that preclude monitoring, and the diuretics should only be monitored under unusual circumstances.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

We describe a method for routinely measuring plasma concentrations of procainamide (PA),N-acetylprocainamide (NAPA) and desethylN-acetylprocainamide (NAPADE) by high-performance liquid chromatography (HPLC). The method has been used together with mass spectrometry of the appropriate chromatographic fraction to demonstrate that NAPADE is a metabolite of NAPA. In addition, comparison of NAPADE concentrations in the plasma of patients receiving PA and NAPA indicates that NAPA is not an intermediate for most of the NAPADE formed from PA. We propose that the principal route of NAPADE formation from PA occurs by initial dealkylation to formp-amino-N-[2-(ethylamino)ethyl]benzamide (PADE), a hypothetical PA metabolite that has yet to be identified.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Phenytoin (PHT) disposition was studied in Greenland Eskimos and in Caucasians (Danes) in order to reveal possible ethnic differences in the pharmacokinetics. PHT was administered i.v. as a single, subsaturation dose to healthy adult volunteers and determined in plasma by thin-layer chromatography. Based on the time/concentration curves obtained, the half-life, volume of distribution, the area under the curve, and the total body clearance were calculated. The protein binding was measured by ultrafiltration. Three groups were studied: Group 1 were Eskimos living in East Greenland, group 2 were Eskimos living in Denmark, and group 3 were comparable Caucasians, as a reference group. The total body clearance of PHT per kg body weight was almost twice as high in Eskimos, irrespective of place of living or sex, compared with the Danish group. The volume of distribution was larger in the Eskimo group, but the protein binding did not differ. The reason for the differences in clearance and volume of distribution between the two ethnic groups is not clear, but the results emphasize that ethnic differences in pharmacokinetics can be of significance. The total body clearance values for PHT in Caucasians found in the present study agreed with results from other European investigations that used the same dose, but different analytical assays.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

In a study of 30 Chinese epileptic children, 43% had poor seizure control. The average daily dose of phenytoin was 6.1 ± 0.53 mg/kg, and the mean plasma level was 4.2 ± 0.63 μg/ml, as determined by the enzyme immunoassay (EMIT®) method. The phenytoin plasma level (μg/ml) versus daily dose (mg/kg) ratios in 73% of these patients were below 1. The average daily dose of phenobarbitone was 5.1 ± 0.36 mg/kg, and the mean plasma level was 24.8 ± 1.7 μg/ml — also estimated by EMIT. Only one patient showed adverse effects. Poor seizure control in patients was chiefly due to subtherapeutic concentrations of phenytoin, which cannot be attributed to poor patient compliance. The presence of phenobarbitone might have accelerated phenytoin metabolism, or the drug could have been lost through sweating. The pharmacokinetics of phenytoin in these Chinese children may be genetically different and might have caused the subtherapeutic phenytoin levels.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The benefits of providing a rapid assay service for phenytoin and carbamazepine were assessed during a 3-month study in an outpatient anticonvulsant clinic. Fifty-three patients were tested using the EMIT® assay system, and a questionnaire was used to compare the physicians' choice of drug dosage and appointment interval before and after each patient result was available. Results were in the therapeutic range for 10 (24%) of the 42 patients on phenytoin and 20 (74%) of the 27 on carbamazepine. The management of 29% of the patients on phenytoin and 22% on carbamazepine was affected, with approximately equal numbers of changes made to dosage (phenytoin 19%, carbamazepine 15%) and appointments (phenytoin 19%, carbamazepine 11%). Of 34 patients with subtherapeutic plasma concentrations, 19 (56%) did not have their doses altered because their seizures were well controlled. Five patients had phenytoin concentrations above 80 μmol/l, but only I had toxic symptoms. The dose was lowered in 2 cases, and 2 more were reduced at the next visit when symptoms of toxicity had developed. It was concluded that both clinical evidence and drug plasma concentrations were considered when making decisions about patient management. The rapid assay service was useful for detecting noncompliers, confirming suspected toxicity, and aiding decision making in doubtful cases.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The clinical use of digoxin and phenytoin analyses (in 405 and 152 patients, respectively) furnished by our clinical pharmacological laboratory during a five-month period was evaluated prospectively from request forms. Of first-time analyses of digoxin, 12, 38, and 50% fell above, within, and below our recommended range of 1.3–2.6 nmoles/liter, respectively. This was a significant change towards lower values compared to an earlier study. The average daily dose of digoxin was 0.22 mg, and 94% of the doses ranged between 0.13 and 0.25 mg. Thirty percent of the patients on digoxin were reinvestigated once or more, and a greater percentage of the concentrations was then within the recommended range. Mean plasma concentrations of digoxin increased significantly with age, even though the stated daily digoxin dose tended to decrease. Data from a drug surveillance study showed that 10 of 32 patients had a significant change in plasma digoxin concentration after admission to hospital, indicating deviations in compliance with the dosage regimen prior to hospitalisation. Sixty-three percent of the first-time analyses of phenytoin were below our recommended therapeutic range of 40–80 μmoles/liter. This was lower than in a previous retrospective investigation (72%). Eighty-seven percent of the doses ranged between 0.2 and 0.4 g/day, and the average daily dose was 0.3 g. High plasma concentrations were noted more frequently in patients aged 60 years or more, whilst low concentrations were noted more frequently in young patients.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Carbamazepine serum levels have been determined by gas-liquid chromatography in 24 children and 26 adults with epilepsy on chronic carbamazepine treatment. A significant correlation has been found between carbamazepine steady-state levels and doses per kilogram body weight in both children (p< 0.01) and adults (p< 0.05). This relationship is characterized by a significant decline in the level/dose ratio with the doses for adults (p< 0.001) and, to a lesser extent, for children (p< 0.05). These results are consistent with a dose-dependent bioavailability.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Concentrations of phenytoin or phenobarbitone have been measured serially using saliva samples in 75 very young children receiving one of these drugs for prevention of recurrent febrile convulsions. Saliva samples were easily obtained and the measured concentrations were a valuable guide to drug dosage during the treatment period.Mean (± SD) saliva concentrations were, for phenytoin, 1.0 ± 0.8 mg/litre (3.8 ± 3.0 μmol/litre) and, for phenobarbitone, 7.9 ± 2.6 mg/litre (34.0 ± 11.3 μmol/litre) and did not alter significantly during the period of observation. Despite frequent review with assessment of compliance, it proved difficult to achieve and maintain target drug concentrations.Paired samples of saliva and plasma were obtained from 36 children before treatment was terminated. Drug concentrations in saliva correlated well with those in plasma and mean plasma: saliva ratios (phenytoin, 8.4; phenobarbitone, 2.2) were comparable to results obtained previously in adults.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

We report here a novel high pressure liquid chromatographic (HPLC) technique for use in therapeutic monitoring of the primary amine antiarrhythmic drug mexiletine in plasma samples. Mexiletine and its structural analogue, the internal standard Ko 768, are extracted with heptane after alkalinization of the sample. The extracts are evaporated to dryness, reconstituted, and injected into a liquid chromatograph equipped with an octadecylsilane reversed phase column using an acetonitrile/acetate buffer mobile phase. Detection is by ultraviolet absorption at 254 nm. The method is linear from 0.2 to 5.0 μg/ml; the coefficient of variation ranges from 5 to 10% within the therapeutic range. The drug is stable for at least 99 days in samples stored at −20°C. Our HPLC results showed good agreement with a popular gas liquid chromatographic method (14), and there are few incidents of interference from common drugs. The method is convenient for any laboratory equipped with standard liquid chromatographic equipment and is suitable for automation.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

A rapid, sensitive, and specific high performance liquid chromatographic (HPLC) method for the quantitative analysis of warfarin in plasma is described. The method involves an extraction from acidified plasma, removal of basic substances, and reextraction into ether. The method is sensitive (0.06–9.0 μg/ml) and precise (coefficient of variation less than 2%) and makes use of a Bondapak C-18 column. Several methods have been reported for the analysis of warfarin; each has some disadvantage in terms of specificity, sensitivity, reproducibility, or convenience. A fluorometric method (1) was rapid, but in our hands was neither precise nor sensitive and yielded values consistently higher than the proposed method. An HPLC method (2) that incorporated a Permaphase column and dioxane as the mobile phase did not perform at all with a Bondapak C-18 column. Gas-liquid chromatography involved derivatization (3), which did not afford reproducibility in our laboratory. Two other published HPLC methods (4,5) showed interference from diazepam. The method described in this paper is specific, accurate, and convenient. It has sufficient sensitivity to measure low warfarin levels, is linear to 9 μg/ml, and is free of interference by common drugs. The clinical utility of this method is illustrated with three case reports.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID