ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03796.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Classification of antiarrhythmic actions is reviewed in the context of the results of the Cardiac Arrhythmia Suppression Trials, CAST 1 and 2. Six criticisms of the classification recently published (The Sicilian Gambit) are discussed in detail. The alternative classification, when stripped of speculative elements, is shown to be similar to the original classification. Claims that the classification failed to predict the efficacy of antiarrhythmic drugs for the selection of appropriate therapy have been tested by an example. The antiarrhythmic actions of cibenzoline were classified in 1980. A detailed review of confirmatory experiments and clinical trials during the past decade shows that predictions made at the time agree with subsequent results. Classification of the effects drugs actually have on functioning cardiac tissues provides a rational basis for finding the preferred treatment for a particular arrhythmia in accordance with the diagnosis.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03797.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Cyclosporine (CsA) dosing is based on CsA plasma or blood concentrations measured 12 to 24 hours after drug administration (trough levels). This study evaluated the relationship between the timing of CsA concentrations and subsequent pharmacokinetic parameters to predict an optimal sampling period. Plasma samples were obtained from 22 patients before their morning dose of CsA and at 2,4,6,8,10, and 12 hours after the dose on the 7th and on the 21st day after heart transplantation. The plasma samples were assayed by both HPLC and FPIA. The Cmax for CsA was achieved over a period ranging from 2 to 6 hours (mean/median = 4.7/4.0) during the day 7 and the day 21 studies. The mean (±SD) half‐life was 3.2 (1.0) hours on day 7 and 2.9 (1.1) hours on day 21, (P>0.05); the mean apparent oral clearance was 276 (117) L/hr on the day 7 and 269 (209) L/hr on day 21, (P>0.05). When CsA plasma concentration by either FPIA and HPLC was monitored, the drug concentration best correlated with AUC was found to correspond to the plasma samples taken 4 to 8 hours after drug administration. The authors conclude that trough blood sampling for therapeutic drug monitoring of CsA is not optimal, and that further studies are necessary to correlate concentration monitoring during the dosing interval with pharmacologic and toxicologic paramete

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03798.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The pharmacokinetics of the enantiomers of etodolac were studied in six young subjects (ages 28 ± 3.3 years), 6 nonarthritic elderly subjects (ages 73 ± 6.0 years), and in three cholecystectomy patients after single oral doses of the racemate (200 mg). In all subjects, the plasma concentrations of R‐etodolac, which is pharmacologically inactive, greatly exceeded those of the pharmacologically active S‐enantiomer. Stereoselectivity was reflected in the pharmacokinetics, with R>S for maximum peak plasma concentration and area under the concentration versus time curve, and S>R for apparent oral clearance and apparent volume of distribution. On average, less than 25% of the dose of each enantiomer was excreted in the urine within 24 hours as alkali‐labile conjugates; little or no unchanged drug was recovered. Bile constituted a minor route of elimination of etodolac as conjugated enantiomers. There were no significant differences in the pharmacokinetics of etodolac enantiomers between the young and elderly subjects. The results reflect the importance of considering stereoselectivity in evaluating the pharmacokinetics of e

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03799.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

A double‐blind randomized parallel group trial was undertaken to compare the acceptability and efficacy of 2 forms of analgesic treatment, DI‐Antalvic (Houde Laboratories, Puteaux, France) (30 mg dextropropoxyphene and 400 mg paracetamol per capsule) and Efferalgan‐Codeine (UPSA Laboratories, Rueil Malmaison, France) (30 mg codeine and 500 mg paracetamol per tablet) prescribed for 1 week at doses of 6 capsules/day and 6 tablets/day, respectively, in 141 outpatients with active osteoarthritis of the knee or hip. The principal aim of the trial was concerned with acceptability, with efficacy as its secondary aim. The principal trial criterion was defined as overall assessment of acceptability by the patient at the end of the trial (success or failure) or by treatment dropouts because of an adverse effect (failure). Comparability of the groups was confirmed before any treatment regarding the physical characteristics of the patients, characteristics of osteoarthritis, and the initial level of pain and functional consequences of pain. Results show that the analgesic efficacy of the treatment was similar, but that the acceptability of Efferalgan‐Codeine was significantly worse than that of DI‐Antalvic: 53% failure with Efferalgan‐Codeine versus 29% failure with DI‐Antalvic (P = .005). Other trials of the same type would seem necessary (comparison of lower doses, other types of pain) before being able to generally extrapolate

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03800.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Relative daytime drowsiness and performance impairment produced by meclizine and dimenhydrinate was assessed in 24 healthy male volunteers. Subjects received either dimenhydrinate, 100 mg, at 8:00am, 12:00pm, and 4:00pm; meclizine, 50 mg, at 8:00am, with placebo at 12:00pmand 4:00pm; or placebo at all three times in this randomized, double‐blind, three‐way crossover study. Impairment of mental performance was assessed by choice reaction time testing and digit symbol substitution scores. Drowsiness was self‐assessed on the Stanford Sleepiness Scale and on a visual analog scale. Both antihistamines produced changes in digit symbol substitution, recognition time, and subjective assessments of sleepiness different from placebo. Expressed as change from baseline, the greatest reductions in digit symbol substitution scores after dimenhydrinate occurred 3 hours after the first dose (6.6 ± 7) and were not different from the greatest measured change after meclizine (5.8 ± 8), which occurred 9 hours after the dose was administered. Similar results were obtained with the other psychometric test scores. Self‐rated sleepiness after dimenhydrinate was greatest 1 hour after the first dose, and was significantly greater than the largest degree of sleepiness after meclizine, which occurred at 7 hours after the dose. The effects of the first dose of dimenhydrinate on psychometric test scores were compared with the magnitude of the effects produced by subsequent doses. The magnitude of effect of the first dose of dimenhydrinate was significantly greater than the magnitude of effect produced by subsequent doses. The data suggest the possibility that acute tolerance to central nervous system impairment develops with multiple doses of dimen

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03801.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The effect of food on the oral bioavailability of sustained‐release morphine sulfate tablets (ORAMORPH SR; Roxane Laboratories, Inc., Columbus, OH; OSR) was examined in an open‐label, randomized, two‐period crossover study. Healthy male volunteers received a 30‐mg OSR tablet orally every 12 hours for seven doses during both the fasted and fed states. Dosing periods were separated by a 14‐day washout Volunteers in the fasted group received all doses either 2 hours before or after meals. Volunteers in the fed group received all doses immediately after meals. All meals were standardized. Serial blood samples were collected for analysis of plasma morphine concentration by radioimmunoassay. Pharmacokinetic parameters were calculated using plasma concentration data collected after the last dose at 72 hours of each dosing period. The two one‐sided t analysis indicated confidence intervals between 80% and 120% for maximum peak plasma concentration (Cmax), AUC72‐84hr, Cavg, and Cmin. The relative bioavailability of OSR administered after meals was 90.2% of that administered in the fasted state. As compared with the fasted condition, morphine bioavailability was essentially unchanged when multiple oral doses of 30‐mg OSR tablets were gi

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03802.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Motion sickness inhibits gastric motility, making the oral route ineffective for medications. The intramuscular route is an effective alternative. The rotating chair was used to produce the M 111 level of motion sickness on the Graybiel Symptom Scale. The intramuscular medications given 30 minutes before rotation were compared with placebo (saline, 1 mL) for effectiveness and duration in increasing the number of tolerated head movements. Average placebo number of head movements was 294. Promethazine 25 mg increased head movements by 78% (P<.05), with a duration of 12 hours. Scopolamine 0.2 mg increased head movements by 91% (P<.05), with a duration of 4 hours. The effect of caffeine 250 mg and ephedrine 25 mg was not significant. When combined with scopolamine, ephedrine produced an 32% additive effect. Scopolamine 0.08 mg, 0.1 mg, and 0.2 mg and also promethazine 12.5 mg and 25 mg were significant (P<.05). Promethazine appears to be the drug of choice for intramuscular use because of a longer duration and a high level of effectiveness. Scopolamine was of high effectiveness, but had a duration of 4 hours. It was eight times as potent by the intramuscular as by the oral route.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03803.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Both classical (atropine, scopolamine) and nontraditional (pirenzepine, telenzepine) cholinolytic agents themselves cause no salivation in human subjects. Ordinarily, they block salivation caused by pilocarpine. Conversely, they all stimulate intense salivatory response in the chronically denervated human parotid gland. The author presents critical comments on the concept that cholinolytic agents cause salivation by suppression of the mechanism of presynaptic autoinhibition. An alternative explanation of the initial cholinomimetic effect of cholinolytic agents is suggested.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03804.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The pharmacokinetics of intravenous and oral nadolol, a long‐acting β‐adrenoceptor blocking agent, were investigated in six children receiving the drug for treatment of supraventricular tachycardia. In the youngest patient (age 3 months), no distribution phase was seen. In children younger than 22 months of age, nadolol is more rapidly eliminated (t1/2 = 4.3 hours or less) than in older children, in whom elimination is more similar to that in adults (t1/2 ∼ 7.3–15.7 hours). After intravenous administration, nadolol displayed two‐compartment pharmacokinetics with a distribution phase (t1/22 = 0.2–1.1 hours) followed by elimination. Large changes in nadolol pharmacokinetics may occur during the first year of life. Nadolol should be used cautiousl

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1992.tb03805.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY