The Significance of Marked “Universal” Dependence of Drug Concentration on Blood Sampling Site in Pharmacokinetics and Pharmacodynamics

Chiou, Win L.

doi:10.1007/978-1-4757-9021-4_4

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…This may also cause volume estimates to differ. 15 In comparing volumes, it is important to note that persistence of the drug in the individual is a function of t 1/2 , and plasma concen-trations maintained during an infusion are a function of clearance. Following extensive surgery, the systemic in¯ammatory response generated may result in oedema.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive care †

Venn

Karol

Grounds

2002

British Journal of Anaesthesia

222

139

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive care †

Venn

Karol

Grounds

2002

British Journal of Anaesthesia

222

139

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Intravenous verapamil kinetics in rats: Marked arteriovenous concentration difference and comparison with humans

Manitpisitkul

Chiou

1993

Biopharm & Drug Disp

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The pharmacokinetics of verapamil, a calcium channel blocker, were studied in male Sprague-Dawley rats following i.v. administration at a dose of 1 mg kg-1. Both arterial and venous blood were collected and the plasma drug concentrations were determined by reversed-phase high-performance liquid chromatography. Verapamil was distributed to the extravascular tissues very rapidly as indicated by the large Vdss (2.99 +/- 0.57 l kg-1) and Vd beta (5.08 +/- 0.54 l kg-1). The apparent terminal plasma T1/2, MRTiv, and CLp were 1.59 +/- 0.46, 1.26 +/- 0.12 h, and 40.4 +/- 9.73 ml min-1 kg-1, respectively. Marked arterial/venous differences were found with a considerable influence on the MRT and Vdss, and the terminal phase venous levels were higher than arterial levels by 103, 69, and 90%, respectively, for the three rats studied. The distribution of verapamil between plasma and erythrocytes occurred very rapidly and was identical in vitro and in vivo. The average blood to plasma and plasma to blood cell concentration ratios were 0.85 and 1.47, respectively. In contrast to propranolol, blood data rather than plasma data should be used to predict the hepatic extraction ratio of verapamil (0.87). The plasma protein binding of verapamil in humans (90%) and rats (95%) were quite similar and constant over the wide concentration range studied. A comparison of some pharmacokinetic parameters between rats and humans is presented and the potential shortcomings of using T1/2 or CLp and the advantage of using CLu (unbound plasma clearance) in interspecies scaling is also discussed.

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Time Course of Drug Effect

Holford¹,

Ludden²

1994

Pharmacokinetics of Drugs

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The Significance of Marked “Universal” Dependence of Drug Concentration on Blood Sampling Site in Pharmacokinetics and Pharmacodynamics

Cited by 3 publications

References 23 publications

Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive care †

Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive care †

Intravenous verapamil kinetics in rats: Marked arteriovenous concentration difference and comparison with humans

Time Course of Drug Effect

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