摘要:

The potential use of saliva in therapeutic drug monitoring cannot be assessed without an understanding of the nature of saliva and how it is collected, the diffusion of drugs across body membranes, and the determinants of a drug's eventual concentration in saliva. For several drugs, saliva concentration will suffice for the derivation of pharmacokinetic data and as an indication of compliance. However, in therapeutic drug monitoring stricter criteria must apply. The saliva concentration must be demonstrably related to drug response, or else reliably and predictably related to the free (unbound) concentration in plasma. Saliva concentrations are usually much lower than plasma concentrations, and quality control is particularly important to ensure accuracy and precision. If reliance is placed upon saliva measurements alone, no error is acceptable which could result in an incorrect therapeutic decision. Only phenytoin and carbamazepine can be considered suitable for therapeutic monitoring in saliva, and saliva sampling is likely to be of clinical value only where venepuncture is difficult or undesirable (e.g., in children), or where the protein binding of phenytoin is abnormal (e.g., renal failure, displacement interactions with other drugs).

ISSN:0163-4356    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

A guiding principle in the use of lithium salts in the treatment of mental illness is to maintain the serum lithium level between 0.8 and 1.2 mmol/L. This article reviews the limited evidence on which such a recommendation is made. The pharmacokinetics of lithium ion and difficulties inherent in serum lithium estimation are briefly examined. Clinical studies which looked specifically for a relationship between lithium dosage and serum concentration are reviewed. Treatment studies of lithium in mania and prophylaxis of affective disorders are assessed for indirect evidence to support a relationship between favorable therapeutic outcome and recommended serum levels.

ISSN:0163-4356    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Although lidocaine has been available for clinical use for 30 years, it still retains an important place amongst antiarrhythmic drugs. It is still widely regarded as the first line of therapy in ventricular arrhythmias occurring after myocardial infarction or cardiac surgery. Recently, however, its use has been advocated in the prophylaxis of primary ventricular fibrillation occurring after myocardial infarction. This recommendation is based primarily on the well-designed and controlled study of Lie and co-workers (1). The results of this study have been reviewed and compared with the results of 11 other studies showing no significant effect of lidocaine in this situation (2). One other study did show that lidocaine gave protection against primary ventricular fibrillation (3). The authors concluded, however, that all the other studies had major defects in trial design, and were prepared to accept the conclusion that lidocaine was effective in preventing primary ventricular fibrillation after myocardial infarction. Similar conclusions were made by De Silva and co-workers (4). As a result, the drug is given in several centres in the U.S.A. to patients admitted with suspected acute myocardial infarction, particularly those aged less than 70 years who are seen within 6 h of the onset of chest pain (5,6).

ISSN:0163-4356    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

A decrease in hepatic clearance and volume of distribution in patients with congestive heart failure frequently leads to toxicity when drugs such as lidocaine are administered. To determine the effect of adjusted dosing of lidocaine in patients with myocardial infarction, we studied 32 patients receiving lidocaine either by a conventional method (control group: 1–2 mg/kg bolus, then 1 to 4 mg/min) or by an adjusted regimen based on the presence or absence of heart failure [experimental group: 1–2 mg/kg bolus; then, class I (no heart failure), 35 to 88 μg/kg/min; class II (heart failure), 12 to 35 μg/kg/min]. Plasma lidocaine levels were determined at 2 and 5 h of the infusion by enzyme multiplied immunoassay technique (EMIT®) and gas liquid chromatography (GLC). Ten of 33 determinations in the control group were in the toxic range, i.e., > 6 μg/ml, and four others were subtherapeutic, i.e., < 2 μg/ml. In contrast, 13 of 16 determinations in the experimental group were in the therapeutic range, and none were in the toxic range. These data show that administration of lidocaine by a conventional method may produce diverse plasma levels that may occasionally be in the toxic range. Modified dosing based on cardiac status may result in optimal levels in most patients.

ISSN:0163-4356    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Plasma disopyramide concentrations were measured in 19 patients with suspected myocardial infarction (MI) following an oral loading dose of 300 mg. Infarction was confirmed in 17 patients. In 10 patients blood samples were collected frequently over a period of 6 h, and in the remaining nine, blood samples were collected for 60 h whilst they were receiving a maintenance dose of 100 mg six hourly. There was a wide variation in the absorption of the drug, and only 8 patients achieved plasma concentrations in the range 2–4 mg/L within one hour of ingestion; 8 of the patients on maintenance therapy were within this range 24 h following the start of therapy. Although only 2 noninfarct patients were observed, they achieved the highest plasma disopyramide concentrations—above the therapeutic range—within 1 h of receiving the loading dose. Narcotic analgesia was associated with poor absorption of the drug, but this does not exclude severity of infarction or vomiting after the loading dose from contributing to the wide variation in plasma concentrations in the early stages following the loading dose. It is concluded that this regime is unsuitable for prophylactic use in acute MI.

ISSN:0163-4356    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Normal adult men with long and short phenytoin plasma half-lives were given 300-mg oral doses of phenytoin once daily for 15 days. Plasma levels of phenytoin (DPH) and its major metabolite (p-HPPH) were measured during the period of drug administration and for 5 days thereafter. Average steady-state plasma levels of DPH rose to 13.4 μg/ml in the long half-life group, compared with 3.6 μg/ml in the short half-life group. HPPH levels in the long half-life group were about one-half of those observed in the short half-life group. The DPH/HPPH ratios in plasma specimens showed excellent correlation with the plasma half-lives of DPH and average steady-state levels, suggesting that this ratio could provide guidance in the selection of optimum dosage regimens for problem patients.

ISSN:0163-4356    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The pharmacokinetics of platinum have been studied in six patients following treatment with cis-dichlorodiammine platinum (CDDP) for metastatic bladder cancer. Each patient received CDDP by 15 min intravenous infusion with total doses ranging from 90 to 120 mg (360 to 480 mg/h). Platinum disposition was biexponential with a relatively rapid distribution and slow elimination. Individual patient elimination half-lives varied from 16.1 to 53.3 h. Although normalized for body weight, individual distribution parameters, V1and Varea, varied from 0.17 to 0.70 L/kg and 0.67 to 1.47 L/kg, respectively. Total body clearance (TBC) also revealed considerable interpatient differences (7 to 40 ml/kg/h). Observed parameter variations could not be explained in terms of existing clinical data. These findings suggest that the pharmacokinetics of platinum in the individual patient might be difficult to predict, and thus serum platinum concentrations should be monitored during cis-dischlorodiammine platinum (II) therapy.

ISSN:0163-4356    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The pharmacokinetics of gentamicin were examined in two functionally anephric patients undergoing peritoneal dialysis (PD). Peritoneal dialysis effectively decreased the gentamicin half-life (t1/2β) by 73 and 78% while increasing total body clearance [QB(ml/min/kg] of gentamicin 4.3– and 3.4-fold. The appreciable variability in gentamicin pharmacokinetics among renal failure patients being peritoneally dialyzed may necessitate dosage adjustments based on rapid and accurate measurement of serum gentamicin concentrations.

ISSN:0163-4356    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

A specific procedure for the analysis of clobazam and N-desmethylclobazam in plasma is described. Reversed-phase liquid chromatography was performed on a Radial-pak cartridge using a mixture of 45% acetonitrile and 55% buffer solution (pH 7); the ultraviolet detector was set at 254 nm. The method used diazepam as internal standard and diethylether as extraction solvent. The calibration curves are linear between 50 and 500 ng/ml for clobazam and between 100 and 1000 ng/ml for /V-desmethylclobazam. The day-to-day precision of the procedure at clobazam plasma concentrations of 50, 250, and 500 ng/ml generated coefficients of variation of 2.2, 6.6, and 11.3%, respectively. No interference occurred in plasma from patients treated with various drugs. The method has been used to study the pharmacokinetics of clobazam and N-desmethylclobazam in patients receiving oral clobazam.

ISSN:0163-4356    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

In this report we describe a rapid and sensitive micromethod using high performance liquid chromatography (HPLC) with electrochemical detection (ED) to measure morphine concentrations in serum or plasma. The separation of morphine and the internal standard, 5-hydroxyquinoline, from interfering compounds present in plasma was achieved by paired-ion reverse phase chromatography using a 70 mM phosphate buffer at pH 5.80. The flow rate was 1 ml/min. Oxidation of morphine and the internal standard was obtained at a potential of 0.60 V. Only 100 μl of serum or plasma was required. Analytical recoveries for morphine and 5-hydroxyquinoline were determined as 78% and 63% respectively. The between-day precision of serum samples containing 250, 100, and 25 μg/L of morphine (n = 20) was 6.5%, 5.2%, and 9.5% respectively. The detection limit was determined as 1 μg/L at a sensitivity of 5 nA/V. In our preliminary studies, 3 children between the ages of 0 and 5 years received a bolus of morphine of 11 μg/kg, followed by an infusion of 2 μg/kg/min during surgery. The time — concentration curves demonstrate an initial rapid fall in morphine concentration with subsequent attainment of a steady state concentration of approximately 90 μg/L after 1 h. This concentration would be expected to produce optimal analgesia in conscious patients.

ISSN:0163-4356    

出版商:OVID    

年代:1982

数据来源: OVID