Plasma levels and tricyclic antidepressant therapy: Part 2. Pharmacokinetic, clinical and toxicologic aspects

Molnár, George; Gupta, Ram N.

doi:10.1002/bdd.2510010602

Cited by 23 publications

(10 citation statements)

References 100 publications

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“…The rapid elimination half-life of amineptine also differentiates it from other tricyclic antidepressants, which have half-lives 10-20 times greater (Molnar and Gupta, 1980). The rapid elimination half-life of amineptine also differentiates it from other tricyclic antidepressants, which have half-lives 10-20 times greater (Molnar and Gupta, 1980).…”

Section: Discussionmentioning

confidence: 98%

Single‐dose Pharmacokinetics of Amineptine and of Its Main Metabolite in Healthy Young Adults

Lachâtre

Piva

Riche³

et al. 1989

Fundamemntal Clinical Pharma

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The pharmacokinetics of the tricyclic antidepressant amineptine (Survector) and its main metabolite were studied in 12 young healthy adults (6 men, 6 women; mean age 35.8 yr). Plasma samples were taken over 24 h following a single oral dose of 100 mg amineptine chloryhdrate. Plasma levels of both compounds were determined by means of high performance liquid chromatography. Amineptine was rapidly absorbed. Mean peak plasma concentrations of amineptine and its metabolite occurred 1 h and 1.5 h, respectively, after product administration. The mean apparent volume of distribution was large: 2.4 l.kg-1. Elimination was rapid; the mean half-lives of the 2 compounds were short: 0.8 h for amineptine and 2.5 h for the metabolite. The mean apparent plasma clearance of amineptine was high (124.8 l.h-1). When the results were adjusted for body weight and surface area, no significant difference in pharmacokinetic parameters was found between men and women. Given its pharmacokinetic characteristics there is no risk of amineptine accumulation and thus it is a particularly easy drug to manage. A standard dosage of amineptine was defined for use in healthy young adults.

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Section: Discussionmentioning

confidence: 98%

Single‐dose Pharmacokinetics of Amineptine and of Its Main Metabolite in Healthy Young Adults

Lachâtre

Piva

Riche³

et al. 1989

Fundamemntal Clinical Pharma

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“…This characteristic differentiates tianeptine from most of the tricyclic antidepressants (Molnar & Gupta 1980) and also non-tricyclics such as zimeldine (Heel et al 1982) and mianserin (Brogden et al 1978). Mean tianeptine AUC was slightly higher than in control subjects but this increase did not attain a statistical significance; this is not surprising for a drug which normally does not undergo substantial first-pass metabolism and which has a bioavailability close to 100% in healthy young subjects.…”

Section: Discussionmentioning

confidence: 99%

“…The drug is extensively metabolised and the renal clearance of unchanged tianeptine is about 0.024 L/h. Nevertheless, first-pass metabolism is extensive with tricyclic antidepressants (Molnar & Gupta 1980), and a small change in this process can greatly affect the amount of the drug reaching the tissues and thus alter drug effect. Nevertheless, first-pass metabolism is extensive with tricyclic antidepressants (Molnar & Gupta 1980), and a small change in this process can greatly affect the amount of the drug reaching the tissues and thus alter drug effect.…”

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confidence: 99%

Tianeptine and its Main Metabolite

Royer

Royer-Morrot

Paille

et al. 1989

Clinical Pharmacokinetics

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The effect of chronic alcoholism (with or without associated moderate cirrhosis) on the disposition of the antidepressant tianeptine, which is devoid of substantial first-pass metabolism, was examined in 21 patients and 11 age-matched controls. Pharmacokinetic parameters for tianeptine and its C5 acid analogue metabolite (MC5 metabolite) were estimated by non-compartmental analysis. The area under the curve (AUC) for tianeptine, following a 12.5mg single oral dose, was decreased by 31% in chronic alcoholics and increased by only 14% in cirrhotics, compared to controls. These changes did not attain statistical significance. The trend of changes in the AUC for the MC5 metabolite was similar to that observed for the parent drug. No statistical difference was found in the terminal half-life for both tianeptine and its MC5 metabolite between patients and controls. On the basis of this study, it appears unnecessary to modify the proposed dosage regimen used in clinical trials (tianeptine sodium salt 12.5mg 3 times daily) in chronic alcoholics with or without associated moderate cirrhosis.

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“…Therefore, numerous studies were designed to explore a relationship between clinical effects and the plasma level of the drug, and of its metabolite, nortripty· line (Nt) (for rev., see 3,7,11,13,19). Therefore, numerous studies were designed to explore a relationship between clinical effects and the plasma level of the drug, and of its metabolite, nortripty· line (Nt) (for rev., see 3,7,11,13,19).…”

Section: Introductionmentioning

confidence: 99%

Quality Control of Amitriptyline and Nortriptyline Plasma Level Assessments

Baumann¹,

Breyer-Pfaff²,

Hj³

et al. 1982

Pharmacopsychiatry

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Numerous studies report about the relationship between the clinical effectiveness of amitriptyline (At) and the plasma level of this drug and of its most important metabolite, nortriptyline (Nt). These agents are therefore very frequently examined for clinical applications and for research programmes in specialized laboratories. The experience with antiepileptic drugs suggests the necessity of quality controls for antidepressants also. Therefore, five institutions in Western Europe performed two such experiments within a year. Two kinds of blood samples were sent for analysis: 1. plasma samples spiked with different quantities of At and Nt from an untreated subject; 2. plasma samples from patients treated with clinical doses of At. Each laboratory happened to use a different analytical method: TLC, HPLC, GC-NPD, GC-FID and GC-MS. The results clearly show the usefulness and the necessity of quality controls for this category of drugs as well. They form the basis for the improvement of the methods of each laboratory in particular. In this context, intralaboratory quality controls are also possible, if one disposes of two different methods. The findings of this study suggest that published reports on relationships between clinical and pharmacological parameters should be considered critically as to possible methodological bias.

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Plasma levels and tricyclic antidepressant therapy: Part 2. Pharmacokinetic, clinical and toxicologic aspects

Cited by 23 publications

References 100 publications

Single‐dose Pharmacokinetics of Amineptine and of Its Main Metabolite in Healthy Young Adults

Single‐dose Pharmacokinetics of Amineptine and of Its Main Metabolite in Healthy Young Adults

Tianeptine and its Main Metabolite

Quality Control of Amitriptyline and Nortriptyline Plasma Level Assessments

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