摘要:

Sixteen subjects completed a two-way crossover study designed to determine the steady-state pharmacokinetic profiles of diazepam and des-methyldiazepam following a 6-mg controlled-release (CR) capsule dosed once daily compared with those of a 2-mg diazepam tablet dosed 3 times a day. Treatment A consisted of 14 days of CR dosing followed by 10 days of tablet dosing. Treatment B was the reverse of Treatment A. Plasma concentrations of diazepam and desmethyldiazepam were determined by an electron-capture gas-liquid chromatographic method. The areas under the diazepam plasma concentration-time curve were similar for both formulations at initiation of dosing and at steady-state, indicating comparable extents of absorption. The mean ratios of the areas at steady-state were near unity — 0.94 for Treatment A and 0.91 for Treatment B — implying that no changes in steady-state conditions occurred upon switching regimens in either direction. The steady-state profiles of desmethyldiazepam were also comparable for the two dosage forms. These data indicate that the CR capsule and the conventional tablet t.i.d. produce similar target concentrations of both the drug and metabolite; therefore, these two dosage forms and dosing regimens should be interchangeable.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

This paper describes an analog computer program used to predict warfarin dosages following an initial three daily doses of 10 mg. The program simulates the patient's response to warfarin and suggested dosages can be entered into the program daily to predict the dose necessary for the patient. Warfarin dosage predictions were made for 29 patients. There was a statistically significant correlation between predicted prothrombin time (PT) response and actual PT response (p < 0.005) for all predictions made. However, when actual and predicted responses were compared with a pairedttest, they were significantly different (p < 0.05). The program described here has been useful for predicting initial warfarin requirements for the majority of patients. Continued research is necessary to identify useful computer methods for predicting warfarin dosages.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The predictive performance of a two-compartment Bayesian forecasting method for lidocaine (L) was evaluated concurrently with lidocaine therapy in 46 hospitalized patients; 14 of these patients presented with congestive heart failure (CHF). Using an HP-85 microcomputer, demographic and dose-concentration information obtained during continuous lidocaine therapy was used to forecast subsequent lidocaine concentrations. One lidocaine concentration was obtained within each of the three intervals following initiation of lidocaine infusions: I1(1–6 h), I2(6–12 h), and I3(>12 h). Patients were categorized into 4 groups: (a) short-term infusions (24 h) without CHF, and (d) long-term infusions with CHF. The mean prediction errors (range −0.60–0.27) included zero (95% confidence limits) in all groups and suggested no bias. Forecasts of the I3lidocaine concentrations were consistently more precise [lower mean absolute errors (MAE) and root mean squared errors] using the lidocaine concentration obtained during the 6–12-h interval (I2) than when the lidocaine concentration obtained at the earlier interval (I1) was used. The MAE was reduced by 20–40% when a single lidocaine concentration obtained during I2was used as compared to I1. Precision was only slightly improved with the use of two lidocaine concentrations. We conclude that this Bayesian algorithm is unbiased and delivers acceptable precision in forecasting lidocaine concentrations.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

A simple, novel approach to phenytoin dose adjustment recently proposed by Wagner has been compared with an established Bayesian method. A data set comprising a minimum of two steady-state concentration/dose pairs from each of 43 adult epileptic patients was used. Prediction error analysis demonstrated that the two methods were equally precise but that the Wagner method tended to underpredict concentrations. The slope of the semilogarithmic relationship between concentration and dose was found to be 54% higher than originally reported by Wagner. It may therefore be necessay to adjust Wagner's equation for different patient populations before this method is used in routine clinical practice.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The predictive ability of a four-point sampling method versus a two-point sampling method for vancomycin was assessed in 11 patients with various staphylococcal infections. All steady-state predictions were based on first-dose pharmacokinetic parameters. The mean vancomycin serum concentrations achieved at 4 and 8 h postinfusion were not significantly different from the predicted concentrations derived from either the four- or two-point method. Also, there was no significant difference between the two methods in predictive ability or accuracy. Both methods underpredicted the steady-state concentration to the same degree, 2.9 μg/ml at 4 h and 3.1 μg/ml at 8 h, which would appear to be clinically acceptable. A one-compartment pharmacokinetic model, which uses two serum concentrations, appears to be adequate for adjusting vancomycin regimens.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The reported biological half-life of the antiarrhythmic drug procain-amide (PA) is between 2 and 4 h. To reassess this, the disposition kinetics of the drug and its pharmacologically active metabolite,N-acetyl procainamide (NAPA), were determined using a newly developed high performance liquid chromatography (HPLC) method. The assay involved extraction from plasma of PA and NAPA with methylene chloride, followed by a brief washing of the extract with water, separation and evaporation of the organic layer, reconstitution in the mobile phase [water/methanol/acetic acid/triethylamine (74:25:1:0.03)], and injection into the HPLC system. At an ultraviolet light detection wavelength of 280 nm, the samples were chromatographed on a reverse-phase column. The minimum quantifiable concentration was 0.005 μg/ml for both the drug and its metabolite. With this sensitivity it was possible to measure PA and NAPA plasma concentrations in samples taken as late as 24 h after single 375-mg oral doses of PA HC1 to 13 healthy volunteers. When only the data points up to 12 h were included in the calculation, the drug t1/2was 3.50 ± 0.82 h (mean ± SD) and in agreement with those reported previously. However, the t1/2became significantly longer (8.52 ± 3.58 h) when the 16− and 24-h data points were also included. The t1/2of NAPA was 8.06 ± 1.33 h and close to the reported values.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

A modified procedure for measuring cyclosporin in whole blood by high-performance liquid chromatography is described and evaluated for clinical use. Sample preparation uses solid-phase extraction cartridges that can be reused. Life of the reverse-phase analytical column exceeds 1,000 injections at 70°C. Cyclosporins A and D (internal standard) elute after 5.6 and 7.6 min, respectively. Calibration plots are linear from 50 ng/ml to at least 2,000 ng/ml. Within-day and between-day imprecision is less than 9% (coefficient of variation). Minimum measurable concentration is 50 ng/ml.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

An isocratic reverse-phase high-performance liquid chromatographic system is described for resolving theophylline, acetaminophen, caffeine, chloramphenicol, ethosuximide, primidone, phenobarbital, phenytoin, and carbamazepine within 7 min. A procedure for routinely measuring these drugs in serum is validated and has been extended to include the quantification ofN-desmethylmethsuximide, barbital, amobarbital, secobarbital, pentobarbital, mephobarbitai, and thiopental. A 250 x 4.6 mm column packed with trimethylsilyl (C-1)-coated 5-μm particles is used. The mobile phase is phosphate buffer (10 mmol/L, pH 6.3):methanol:acetronitrile, 65:17.5:17.5. A common solvent extraction procedure is used for all of these drugs. The extractant is choloroform:isopropanol (95:5), containing three internal standards: 3-isobutyl-1-methylxanthine (IMX), tolybarb, and methsuximide. Theophylline, acetaminophen, caffeine, and chloramphenicol are quantified at 273 nm with IMX as the internal standard. With two exceptions, the rest of the drugs are quantified at 204 nm using tolybarb as the internal standard; ethosuximide is quantified at 204 nm using methsuximide as the internal standard, and thiopental is quantified at 285 nm using IMX as the internal standard.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID