Twenty depressed patients seen in general practice were admitted to an open, uncontrolled pilot trial of a new 50 mg formulation of clomipramine. Treatment was administered for four weeks and clinical progress assessed by the General Health Questionnaire, a new depression rating scale and a new design of a visual analogue scale. Two patients dropped out of the study, one because of side-effects and a second because it was necessary to change the dosage. Of the 18 patients remaining 17 showed significant improvement during the four weeks treatment as assessed by the three clinical measures. Plasma levels of clomipramine and desmethylclomipramine were assayed. Steady-state appeared to be achieved between one and two weeks. Between two and four weeks levels of clomipramine varied between 14 and 136 microng/ml with a mean level of 54-6 microng/ml and of desmethylclomipramine, between 3-5 and 344-3 microng/ml with a mean level of 76-7 microng/ml The 50 mg formulation of clomipramine appeared to produced therapeutic levels in 17 of the 18 patients treated. Because so many patients recovered in spite of individually variable plasma levels no correlations between clinical effect and plasma levels were demonstrable. Side-effects were not generally troublesome and were low in incidence. Correlations between plasma level and side-effects were inexplicably negative but rarely significantly so.

Adult↗

PubMed1977

Factors influencing plasma drug concentrations.

The usefulness of measuring plasma concentrations of drugs in patients is now well established and permits a greater efficacy and safety of treatment since dosage can be adjusted on an individual basis. In monitoring plasma concentrations one must recognize that a number of factors may influence these levels. For instance, levels may be affected by age, body-weight and size, genetical factors, abnormalities of water and electrolyte balance and complications associated with pathological conditions such as renal and hepatic impairment. Likewise, plasma levels will depend on dosage, time and route of drug administration, the bioavailability of the drug and time of blood sampling. In addition, absorption, distribution, metabolism, excretion and concurrent drug administration may profoundly affect plasma drug concentrations.

Age Factors↗

PubMed1977

Plasma level studies with clomipramine (anafranil)

Patients showing symptoms of depressive illness were treated in general practice with one of four clomipramine (Anafranil) dosage regimes (25 mg t.d.s., 75 mg o.n., 10 mg t.d.s. and 30 mg o.n.). Blood was sampled on admission to the study and at days 7, 14 and 28. Plasma analysis revealed that steady-state concentrations of clomipramine and its main metabolite desmethyclomipramine were reached at day 7 of treatment in each of the dosage groups. No apparent relationship between dosage and plasma level of clomipramine was found in this study since there was no significant difference between mean steady-state plasma levels in each of the four dosage regimes. In contrast, plasma concentrations of desmethylclomipramine appeared to be directly related to the dose of clomipramine administered. Intersubject variations in plasma levels of the parent compound within each dosage group ranged from three to fourteen-fold.

Adult↗

PubMed1976

Preliminary studies on the absorption, distribution and excretion of N-(2-hydroxyethyl)-maleopimarimidyl morpholide (3H-RU 18492) in the female rat and dog.

Following the oral administration of 3H-labelled N-(2-hydroxyethyl)-maleopimarimidyl morpholide (3H-RU 18 492) to rats and dogs, radioactivity was detected in plasma and the various tissues examined. However, the major fraction of the dose remained unabsorbed and the highest concentrations of radioactivity were found in the liver. In both species the major route of excretion of radioactivity was via the bile.

Animals↗

PubMed1976