Drug Absorption and Metabolism Studies by Use of Portal Vein Infusion in the Rat. II. Influence of Dose and Infusion Rate on the Bioavailability of Propranolol

Suzuki, Takahito; Isozaki, Sadao; Ishida, Ryosuke; Saitoh, Yurika; Nakagawa, Fujio

doi:10.1248/cpb.22.1639

Cited by 25 publications

(8 citation statements)

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“…3). Such results were previously also observed for propranolol [Suzuki et al, 1972[Suzuki et al, , 1974[Suzuki et al, , 1980. It is important to note that the non linearity in the kinetics of hexobarbital was not recognized in the blood concentration versus time curves of the present experi ments, because these always showed a loglinear course during the elimination phase.…”

Section: Discussionsupporting

confidence: 85%

Influence of the Rate of Hepatic Portal Vein Infusion on Hexobarbital Pharmacokinetics in the Rat

1988

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Pharmacokinetic parameters of hexobarbital were estimated in rats after hepatic portal infusion of a 10-mg dose. Infusion during 10 min resulted in an area under the blood concentration-time curve (AUC) of 556 ± 83 μg·min/ml and a clearance of 83 ± 13 ml/min·kg, whereas infusion of the same dose during 40 min resulted in values of 272 ± 36 μg·min/ml and 169 ± 30 ml/min·kg, respectively (mean values ± SD, n = 3). Infusion during 15 and 20 min provided intermediate values. The decrease of the AUC and the increase of the blood clearance of hexobarbital following decreasing infusion rates clearly indicate nonlinear pharmacokinetics related to the hepatic inflow concentration of hexobarbital.

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Section: Discussionsupporting

confidence: 85%

Influence of the Rate of Hepatic Portal Vein Infusion on Hexobarbital Pharmacokinetics in the Rat

1988

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“…Furthermore, the bioavailability of an 80-mg oral dose in several subjects varied from 16 to 60% of that of a 10-mg iv dose. The variations in blood levels as well as the low bioavailability from oral doses have been attributed to extensive drug metabolism during absorption and first passage through the liver (1)(2)(3). A previous report (4) indicated that the blood levels of propranolol after intravenous and nasal administration of 1-mg doses in rats were identical but that oral administration of the same dose resulted in considerably lower blood levels.…”

mentioning

confidence: 99%

“…Phenylbutazone is highly protein bound (-99%) (1). The drug is eliminated mainly in the urine (60-70%) (1,2).…”

mentioning

confidence: 99%

Nasal absorption of propranolol from different dosage forms by rats and dogs

Hussain

Hirai

Bawarshi

1980

Journal of Pharmaceutical Sciences

135

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“…The rate of presentation of propranolol to the liver can effect resulting systemic bioavailability presumably as a result of saturation of hepatic metabolism. 7 This may partially explain the suggestion of increased exposure following ileal dosing. Increased rate of absorption from Significantly increased propranolol exposure resulted from endoscopic delivery to the stomach than from conventional gavage.…”

Section: Discussionmentioning

confidence: 99%

Site-specific Drug Delivery in the Dog using Flexible Fiberoptic Endoscopy

Heit¹,

Smith²,

Enever³

1998

Journal of Pharmaceutical Sciences

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The development of a nonsurgical repeatable method of site-specific delivery to the gastrointestinal tract in the canine is described. Studies to characterize and validate this method were performed utilizing propranolol and etodolac due to their well-known pharmacokinetic properties. Using a catheter placed through the auxiliary port of a flexible fiberoptic endoscope, liquid dosage formulations were consistently delivered to the canine stomach, duodenum, ileum, and colon. It was shown that differences in site-specific delivery could be demonstrated with this model. Propranolol tended to have the highest exposure following dosing to the ileum as compared to other sites. The anesthetic regimen used to perform endoscopy affected certain pharmacokinetic parameters of the compounds being tested including decreasing the intrinsic clearance of propranolol. However, since decreased intrinsic clearance should similarly affect AUCo regardless of the site of delivery, this does not preclude site-specific comparisons to be made. Further, no evidence has been reported for the effect of anesthesia on one GI segment but not another. Thus for other compounds, assuming there are either no anesthetic effects on intestinal pharmacokinetic parameters (absorption, intestinal metabolism, etc.) or that they are consistent and uniform throughout the intestinal tract, this model allows comparisons of the exposure following delivery to differing intestinal sites.

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Drug Absorption and Metabolism Studies by Use of Portal Vein Infusion in the Rat. II. Influence of Dose and Infusion Rate on the Bioavailability of Propranolol

Cited by 25 publications

References 0 publications

Influence of the Rate of Hepatic Portal Vein Infusion on Hexobarbital Pharmacokinetics in the Rat

Influence of the Rate of Hepatic Portal Vein Infusion on Hexobarbital Pharmacokinetics in the Rat

Nasal absorption of propranolol from different dosage forms by rats and dogs

Site-specific Drug Delivery in the Dog using Flexible Fiberoptic Endoscopy

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