Food effects on propranolol systemic and oral clearance: Support for a blood flow hypothesis

Olanoff, Lawrence S.; Walle, Thomas; Cowart, T. Douglas; Walle, U K; Oexmann, Mary Joan; Conradi, Edward C.

doi:10.1038/clpt.1986.198

Cited by 64 publications

(42 citation statements)

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“…However, the effect of food may be explained by the rate of gastric emptying, since food can delay gastric emptying, thereby increasing the available time for absorption. Food may also increase mesenteric blood flow and enhance absorption; this increased mesenteric blood flow might also cause decreased 'first pass' hepatic clearance by creating functional shunts in the liver [9]. To date, there is no information suggesting that MK-0476 is a 'high clearance' drug susceptible to this effect.…”

Section: Analysis Ofpharmacokinetic Datamentioning

confidence: 93%

Single dose pharmacokinetics, safety and tolerability of MK‐0476, a new leukotriene D4‐receptor antagonist, in healthy volunteers.

Schoors¹,

Smet²,

Reiss³

et al. 1995

Brit J Clinical Pharma

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acetate is a novel, potent, and specific LTD4-receptor antagonist. The safety, tolerability and plasma drug profiles of single oral doses of MK-0476 (capsules) were evaluated in 18 healthy male volunteers assigned to one of the two parallel 9-subject panels. Under fasting conditions, increasing single doses of 20 to 800 mg were administered in a first part of the study and in a second part, 200 mg MK-0476 was given either as a solution, under fasting conditions, or as capsules, after a standard breakfast. All volunteers completed the study. Side effects, reported by the investigator to be related to study drug, were mild and transient. No laboratory abnormalities were noted. In the evaluated dose range of MK-0476 (20 to 800 mg) the median value of tmax ranged from 2 to 4 h, while the apparent ti,2 value averaged 4 to 5 h. The median tmax value of the 200 mg capsule dose was not significantly different from the median tmax of the 200 mg oral solution dose indicating that neither disintegration nor dissolution is a rate-limiting step for the absorption of MK-0476 from capsules. There was a statistically significant increase in the AUC (geometric mean ratio of fed/fast was 2.52 with 95% confidence interval of 1.25, 5.06) and in Cmax (geometric mean ratio of fed/fast was 1.36 with 95% confidence interval of 0.60, 3.04) when MK-0476 was given together with a breakfast, suggesting an increase in bioavailability. We conclude that single oral doses of MK-0476 (range 20 to 800 mg) appear to be well tolerated and both formulations (capsule and solution) achieve similar plasma concentrations.

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Section: Analysis Ofpharmacokinetic Datamentioning

confidence: 93%

Single dose pharmacokinetics, safety and tolerability of MK‐0476, a new leukotriene D4‐receptor antagonist, in healthy volunteers.

Schoors¹,

Smet²,

Reiss³

et al. 1995

Brit J Clinical Pharma

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“…The mechanism by which food increases the bioavailability of praziquantel remains to be demonstrated. The effect could be related to tablet disintegration, better drug dissolution, or other factors, such as changes in hepatic blood flow or in the metabolism of the drug during the first passage through the liver (5)(6)(7)(8). Considering that both treatments had a high carbohydrate content, it is possible that carbohydrates had the major influence on the bioavailability of praziquantel.…”

mentioning

confidence: 99%

Bioavailability of Praziquantel Increases with Concomitant Administration of Food

Castro

Medina

Sotelo

et al. 2000

Antimicrob Agents Chemother

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In the present study we found that after a single oral dose of 1,800 mg of praziquantel, following a high-lipid diet and a high-carbohydrate diet, the maximum levels in plasma increased 243 and 515% and the area under the plasma concentration curve from 0 to 8 h increased 180 and 271%, respectively.Nine healthy volunteers participated in the study. The mean age was 33.44 years (range, 26 to 47 years), and the mean weight was 72.22 Ϯ 11.29 kg. The protocol was approved by the local ethics committee, and informed written consent was obtained from each subject after detailed explanation of the purpose and risks of the study. Subjects did not take any other medication or alcohol for at least 15 days prior to the study.Volunteers were randomly separated into three groups of three subjects each. Group I received three tablets of 600 mg of praziquantel (1,800 mg) after 10 h of fasting; group II received the same dose of praziquantel immediately after administration of a high-fat diet, and group III received the same dose of praziquantel after a high-carbohydrate diet. Volunteers received a standard lunch 4 h after drug ingestion. The study was repeated in a crossover design allowing 1 week of washout between treatments. Blood samples were obtained through an indwelling catheter placed in the antecubital vein 0.0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, and 8.0 h after the drug administration. Samples were centrifuged; the plasma was separated and stored at Ϫ4°C until analysis.The high-fat diet consisted of two fried eggs, one slice of ham, orange juice, and milk (200 ml) (protein, 19.63%; fat, 32.44%; and carbohydrate, 47.91%; 656 cal); the high-carbohydrate diet consisted of four tortillas, tomato, chicken (100 g), a slice of white bread, and a glass (200 ml) of orange juice (protein, 15.30%; fat, 10.54%, and carbohydrate, 74.15%; 674.5 cal).Praziquantel in plasma was determined using a high-performance liquid chromatography assay as previously reported (1). The method was linear from 15.6 to 8,000 ng/ml. The limit of quantitation was 15.6 ng/ml. The maximum within-day coefficient of variation was 7.9% at 15.6 ng/ml, and the mean value FIG. 1. Mean concentration in plasma (ϩstandard error of the mean) of praziquantel in healthy volunteers treated with a single oral dose of 1,800 mg (three tablets of 600 mg) during fasting (F) or immediately after a high-fat (‚) or a high-carbohydrate (s) breakfast.

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“…The postprandial increase in systemic clearance of i.v. drugs having high hepatic clearance is well known and is mainly explained by an increased hepatic blood flow [19]. However, because the effect of food on hepatic blood flow was not assessed in the present trial, the PK model estimates the food effect on the clearance based on the observed concentration data.…”

Section: Pharmacokinetic/pharmacodynamic Modellingmentioning

confidence: 99%

Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects

Nicolas

Krause

Gutierrez

et al. 2012

Brit J Clinical Pharma

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Of the two metabolites analyzed, the appearance of 6-keto-prostacyclin F(1α) in plasma was more closely associated with the haemodynamic effects of i.v. epoprostenol. PK and PD profiles showed that CIn relates proportionally and linearly to the plasma concentrations of 6-keto-prostacyclin F(1α) . These results suggest that 6-keto-prostacyclin F(1α) is a suitable surrogate marker of plasma concentrations of epoprostenol.

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Food effects on propranolol systemic and oral clearance: Support for a blood flow hypothesis

Cited by 64 publications

References 0 publications

Single dose pharmacokinetics, safety and tolerability of MK‐0476, a new leukotriene D4‐receptor antagonist, in healthy volunteers.

Single dose pharmacokinetics, safety and tolerability of MK‐0476, a new leukotriene D4‐receptor antagonist, in healthy volunteers.

Bioavailability of Praziquantel Increases with Concomitant Administration of Food

Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects

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