摘要:

A clinical trial comparing ibuprofen, 400, 600, and 800 mg, with aluminum ibuprofen, 400 mg, and placebo was conducted in patients with moderate or severe pain subsequent to third molar extraction. Pain intensity ratings and ibuprofen serum levels were obtained at baseline, 30 minutes, 1 hour, and hourly thereafter for 3 hours. Pain intensity ratings were also obtained at hours 4, 5, and 6. Serum levels at 1, 2, and 3 hours correlated significantly with the log dose of ibuprofen (r = 0.35, 0.49, and 0.48, respectively) and with global analgesic response as measured by the percentage of the sum of the pain intensity scores (r = 0.28, 0.34, and 0.26, respectively). However, possibly because of differences in drug formulation, the percentage of the sum of the pain intensity scores did not correlate significantly with log dose. The highest correlations were found between contemporaneous serum levels and pain intensity difference values, particularly at hour 1 (r = 0.54). Our results support the proposition that increased ibuprofen serum levels lead to increased analgesia.Clinical Pharmacology and Therapeutics(1986)40,1–7; doi:10.1038/clpt.1986.1

ISSN:0009-9236    

DOI:10.1038/clpt.1986.129

年代:1986

数据来源: WILEY

摘要:

The response to imipramine (IMI) in children with depression has been shown to correlate with total levels of IMI plus its active metabolite desmethylimipramine (DMI). The pharmacokinetics of IMI + DMI in children with depression are examined, and the single‐point prediction of steady‐state IMI + DMI levels at minimum therapeutic concentrations for prepubertal depression is proposed. With a single, 25 mg oral dose of IMI, a plasma concentration of IMI + DMI 24 hours after dosing correlates (r = 0.92) with steady‐state IMI + DMI levels in children with depression receiving 3 mg/kg/day IMI. The targeting of IMI dose in the child population with depression to rapidly achieve a minimum therapeutic concentration is shown to be feasible and reliable within theoretic limits.Clinical Pharmacology and Therapeutics(1986)40,8–13; doi:10.1038/clpt.

ISSN:0009-9236    

DOI:10.1038/clpt.1986.130

年代:1986

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1986)40,13–13; doi:10.1038/clpt.1986.1

ISSN:0009-9236    

DOI:10.1038/clpt.1986.131

年代:1986

数据来源: WILEY

摘要:

Factors that influence intersubject variability in response to furosemide have been investigated in normal subjects and patients with cirrhosis. Furosemide pharmacokinetics and pharmacodynamics were measured in eight normal subjects and 14 patients with cirrhosis, eight of whom were resistant to diuretic therapy. Furosemide renal clearance decreased in proportion to creatinine clearance, whereas nonrenal clearance and volume of distribution were unchanged. These pharmacokinetic changes were, however, minimal and resulted in an only marginal alteration in the plasma concentration‐time curve. The maximal rate of urinary sodium excretion decreased with reductions in creatinine clearance (r = 0.77). However, the extent of reduction in urinary excretion of sodium was proportionally greater than the reduction in creatinine clearance, whereas the rate of urinary furosemide excretion required to achieve 50% of maximal response did not change. Furosemide's pharmacokinetics were not, therefore, appreciably altered by cirrhosis. However, cirrhosis was associated with a reduction in pharmacodynamic response to this diuretic.Clinical Pharmacology and Therapeutics(1986)40,14–20; doi:10.1038/clpt.1986

ISSN:0009-9236    

DOI:10.1038/clpt.1986.132

年代:1986

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1986)40,20–20; doi:10.1038/clpt.1986.1

ISSN:0009-9236    

DOI:10.1038/clpt.1986.133

年代:1986

数据来源: WILEY

摘要:

The pharmacokinetics and hemodynamic effects of nifedipine were studied in patients with liver cirrhosis and in age‐matched healthy control subjects. In a randomized order each subject received nifedipine by intravenous infusion (4.5 mg in 45 minutes) and as a tablet (20 mg). After intravenous nifedipine patients had a longer elimination t½(420 ± 254 vs. 111 ± 22 minutes; P<0.01), a greater volume of distribution (1.29 ± 0.60 vs. 0.97 ± 0.42 L/kg), and a lower systemic clearance (233 ± 109 vs. 588 ± 140 ml/min; P<0.001). Plasma protein binding of nifedipine was lower in the patients (P<0.001). After oral nifedipine systemic availability was much higher in patients (90.5% ± 26.2% vs. 51.1% ± 17.1%; P<0.01) and maximal in patients with a portacaval shunt. Blood pressure decreased and heart rate increased after intravenous nifedipine and these effects could be fitted to plasma concentrations by a sigmoidal model. Maximal effects on heart rate and diastolic blood pressure were not different in liver cirrhosis. When free drug levels were considered, the concentrations corresponding to half the maximal effect were also not different. Blood pressure changes with oral nifedipine were comparable with those after intravenous infusion. We conclude that in patients with liver cirrhosis the pharmacokinetics of nifedipine are considerably altered; dose reduction is recommended when such patients need oral nifedipine.Clinical Pharmacology and Therapeutics(1986)40,21–28; doi:10.1038/

ISSN:0009-9236    

DOI:10.1038/clpt.1986.134

年代:1986

数据来源: WILEY

摘要:

The influence of concomitant food intake on the bioavailability and presystemic primary conjugation of propranolol (80 mg) was studied in 11 healthy women. Food increased the maximum serum concentration and serum AUC of propranolol (P<0.05) and reduced those of conjugated propranolol (P<0.05). The mean AUC ratio of conjugated/unchanged propranolol was 13:1 in the fasting state but only about 6:1 in the nonfasting state (P<0.001). The time to maximum serum concentration and the t½were not affected by food. There was no influence of food on any kinetic parameter of propranolol or conjugated propranolol when a slow‐release formulation was used. We conclude that concomitant food intake can evoke a short‐lasting, delivery rate—dependent inhibition of the presystemic primary conjugation of propranolol. This is one, but not the sole, mechanism by which food can enhance propranolol bioavailability.Clinical Pharmacology and Therapeutics(1986)40,29–36; doi:10.1038/clpt

ISSN:0009-9236    

DOI:10.1038/clpt.1986.135

年代:1986

数据来源: WILEY

摘要:

Enprostil, an orally active prostaglandin E2analog, is undergoing clinical trials in the treatment of peptic ulcer disease. Because results of animal studies suggested that prostaglandins might affect both hepatic drug metabolizing ability and hepatic blood flow, the effects of enprostil on drug elimination were studied and compared with those of the standard antiulcer drug Cimetidine in a double‐blind, randomized, crossover study of nine normal subjects. Cimetidine reduced the oral clearance of propranolol by 50%, consistent with the inhibition of drug metabolism reported in previous studies. On the other hand, enprostil had no effect on propranolol elimination. Neither drug altered liver blood flow as assessed either by the clearance of indocyanine green or by the technique of dual route of administration of propranolol. Thus in contrast to cimetidine, enprostil had no effect on hepatic drug metabolism.Clinical Pharmacology and Therapeutics(1986)40,37–41; doi:10.1038/clpt.1986

ISSN:0009-9236    

DOI:10.1038/clpt.1986.136

年代:1986

数据来源: WILEY

摘要:

The antihypertensive effect of transdermal nitroglycerin was tested in 11 men with hypertension (mean age 60 years) whose diastolic blood pressure exceeded 90 mm Hg while receiving a diuretic and a β‐adrenergic blocker. In a double‐blind, randomized crossover trial the subjects received weekly increments of placebo or nitroglycerin (5, 10, 20, and 30 cm2) for 4 weeks each. The final dose of nitroglycerin was 22.5 cm2(mean). During week 4 of nitroglycerin dosing, sitting and standing systolic blood pressures were reduced (P<0.05). Diastolic blood pressures and heart rates did not change during the study. In the five subjects with systolic hypertension (≥150 mm Hg), the mean reduction in systolic blood pressure was 24 mm Hg (P<0.01). Further studies are needed to determine if transdermal nitroglycerin has a role in the treatment of systolic hypertension.Clinical Pharmacology and Therapeutics(1986)40,42–45; doi:10.1038/clpt

ISSN:0009-9236    

DOI:10.1038/clpt.1986.137

年代:1986

数据来源: WILEY

摘要:

The effect of fibrosis on drug metabolism in alcoholic liver disease was evaluated in a comparison of the concentrations of serum aminoterminal propeptide of type III procollagen and basement membrane (BM;7Sdomain of type IV collagen and laminin) antigens with in vitro (cytochrome P‐450) and in vivo (antipyrine) drug metabolism in 67 alcoholics classified by liver histology. Alcoholics with intact or fatty liver had rapid or normal drug metabolism and normal collagen metabolism. Alcoholics with a fatty liver plus fibrosis or active cirrhosis had reduced drug metabolism and elevated levels of serum markers for collagen and BM metabolism. Alcoholics with inactive cirrhosis who had received therapy with enzyme inducers had a tendency toward normal drug and collagen metabolism parameters. Antipyrine metabolism, but not P‐450 content, was related to the levels of serum type III collagen and BM markers. The fibrotic process, especially BM formation, creates a mechanical barrier that may prevent contact between blood and hepatocytes, thus delaying substrate availability.Clinical Pharmacology and Therapeutics(1986)40,46–55; doi:10.1038/clpt.19

ISSN:0009-9236    

DOI:10.1038/clpt.1986.138

年代:1986

数据来源: WILEY