Entry of quinidine into cerebrospinal fluid

doi:10.1016/0002-8703(80)90148-9

American Heart Journal

Volume 100, Issue 3, September 1980, Pages 341-346

https://doi.org/10.1016/0002-8703(80)90148-9 Get rights and content

Abstract

Some of the unwanted effects of quinidine commonly occurring in clinical practice involve the central nervous system. We therefore assessed the rate and extent of quinidine passage into cerebrospinal fluid (CSF) in humans and dogs. In eight human subjects receiving oral quinidine therapy, lumbar CSF quinidine concentrations averaged 16% of unbound serum concentrations (range: 4% to 37%). The findings were confirmed when simultaneous serum (total and unbound) and CSF quinidine concentrations were followed for up to 8 hours after a single intravenous dose of quinidine in anesthetized dogs. Quinidine appeared promptly in CSF of all animals, but CSF concentrations averaged only 37% to 46% of unbound serum levels. The in vitro octanol: water partition coefficient for quinidine at physiologic pH was greater than 100, indicating that unbound quinidine should readily traverse the blood-brain barrier. Thus, passage of quinidine into CSF appears not to be governed by passive diffusion alone. Quinidine may participate in an active transport system such as that which removes certain other basic substances from CSF.

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^☆: Supported in part by Grants MH-12279 (Dr. Greenblatt) and HL-18003 (Dr. Smith) from the United States Public Health Service

^☆☆: This work was done in part during the tenure of the following research grant-in-aid awards (to Dr. Greenblatt): No.13-056-756 from the American Heart Association, Western Massachusetts Division and the American Heart Association, Massachusetts Affiliate, Inc.; and No.13-512-767 from the American Heart Association, Central Massachusetts Division.

¹: Dr. Ochs was supported by Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, West Germany.

^∗: Present address: Royal Perth Hospital, Perth, W. Australia.

²: Dr. Lloyd was an Overseas Fellow of the National Heart Foundation of Australia.

^∗∗: Present address: Massachusetts Rehabilitation Hospital, Boston.

³: Dr. Woo was the recipient of a research fellowship (No. HL-05723) from the United States Public Health Service.

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Experimental and laboratory reportEntry of quinidine into cerebrospinal fluid☆,☆☆

Abstract

Progr. Cardiovasc. Dis.

Side effects of antiarrhythmic drugs

Naunyn Schmiedebergs Arch. Pharmakol.

Quinidine toxicity: a review

Rocky Mt. Med. J.

Antiarrhythmic agents

Quinidine dementia

J.A.M.A.

Quinidine overdose: neurological and cardiovascular toxicity in a normal person

Br. Heart J.

Pharmacokinetics of quinidine in humans after intravenous, intramuscular and oral administration

J. Pharmacol. Exp. Ther.

The mechanism of vomiting induced by quinidine. II

J. Pharmacol. Exp. Ther.

Distribution between blood and cerebrospinal fluid: general methodology and effect of pH gradients

J. Pharmacol. Exp. Ther.

The blood-cerebrospinal fluid barrier in man

Arch. Neurol.

The importance of dissociation constant and lipid-solubility in influencing the passage of drugs into the cerebrospinal fluid

J. Pharmacol. Exp. Ther.

Kinetics of penetration of drugs and other foreign compounds into cerebrospinal fluid and brain

J. Pharmacol. Exp. Ther.

Lipid solubility and drug penetration of the blood brain barrier

Blood-brain barrier: penetration of morphine, codeine, heroin, and methadone after carotid injection

Science

Blood-brain barrier permeability to drugs

Ann. Rev. Pharmacol.

Experimental and laboratory report
Entry of quinidine into cerebrospinal fluid☆,☆☆