Elsevier

Biochemical Pharmacology

Volume 18, Issue 9, September 1969, Pages 2135-2143
Biochemical Pharmacology

Plasma protein binding of tricyclic anti-depressants in man

https://doi.org/10.1016/0006-2952(69)90318-9Get rights and content

Abstract

The binding of various tricyclic antidepressants to human plasma and the effects thereupon of other drugs were studied by an ultrafiltration technique utilizing labeled compounds. At a total concentration of 0·29 μ/ml the percentage of unbound desmethylimipramine(DMI) was found to be 9·5 ± 1·4 in 41 individuals. The unbound fraction of DMI in plasma increased only twofold when the total concentration of the drug was increased a thousand times. The degree of binding over the entire range of therapeutic plasma drug concentration was relatively constant.

The binding of various tricyclic antidepressants was compared at a drug concentration of 1·1 μM. The percentage of unbound drug was for nortriptyline (NT) 5·5 ± 0·6, for amitriptyline (AT) 3·6 ± 0·8, for imipramine (I) 4·2 ± 0·8, for protriptyline (PT) 8·0 ± 0·6 (tested at a cone, of 7·7 μM) and for Leo 640, an imipramine analogue, 0·7 ± 0·7. The acetyl derivatives of DMI, NT and PT were much more bound than the parent compounds. The addition of NT, PT or AT in a “therapeutic” concentration of 0·2 μg/ml didnot displace DMI, nor did chlorpromazine in supratherapeutic concentration. Diphenylhydantoin was found to displace DMI, NT, PT, AT and particularly I.

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Fulbright Scholar. Permanent address: University of Kansas Medical Center, Kansas City, Kansas, U.S.A.

Permanent address: AB Leo, Hälsingborg, Sweden.

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