Mario Furlanut

Pharmacokinetic Optimisation of Tricyclic Antidepressant Therapy

SummaryPharmacokinetics has greatly contributed to the elucidation of the variability in clinical response to antidepressants in terms of differences in plasma concentrations due to genetic constitution, age, associated diseases and drug interactions. Despite no general agreement, therapeutic and toxic concentrations have been suggested for some tricyclic antidepressants (TCAs) [ami-triptyline, nortriptyline, imipramine, desipramine]. Predictive techniques may be implemented on the basis of which starting TCA dosages may be selected to reach more rapidly those concentrations at which efficacy is more probable. Therapeutic drug monitoring may thereafter assist the clinician in refining the individualisation of the dosage regimen.

Effects of papaverine and eupaverin on calcium uptake by isolated sarcoplasmic vesicles

Papaverine and eupaverin increase the rate of uptake of calcium by sarcoplasmic vesicles isolated from rabbit white skeletal muscle. The degree of activity of the above drugs is clearly affected by changes of ATP, oxalate and Ca2+ concentrations. The results are discussed in view of present knowledge about the effects of papaverine‐like drugs upon muscular contraction.

Effects of some spasmolytic agents on the Iipid‐facilitated transport of calcium ions

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The effects of dose, age, and sex on the serum levels of phenobarbital and diphenylhydantoin in epileptic patients

Summary Serum levels of phenobarbital and diphenylhydantoin were monitored in epileptic patients chronically treated with anticonvulsants. A satisfactory relationship was found between dose (mg/Kg body weight) and serum concentrations of phenobarbital (r = 0.75). No such correlation was present with diphenylhydantoin (r = 0.45). Multiple positive correlation was demonstrated for the two above anticonvulsants between dose, serum levels and age in females.

Interaction between dibucaine and K+ on smooth muscle

Summary The effect of dibucaine on electrical and mechanical activity of taenia coli has been studied. The myolytic activity of dibucaine is accompanied by the appearance of large regular spikes coupled to rhythmic phasic contractions. Furthermore dibucaine induces a reversal of the mechanical response to acetylcholine. The effect of dibucaine have been relateed to an interference with potassium fluxes across the membrane of smooth muscle.

Carbamazepine and carbamazepine-epoxide serum concentrations in some resistant cases of complex partial seizures

Sir, In epileptic patients on carbamazepine (CBZ) therapy a worsening of seizures may sometimes be observed after a limited period of apparent response. Autoinduction [1, 2] may be the cause of this. In order to verify this hypothesis we carried out an investigation in 6 patients (3 males and 3 females) from 17 to 25 yrs, affected by complex partial seizures apparently resistant to anticonvuisants. None had hepatic or renal diseases. At the beginning, the patients were on polytherapy (5 CBZ+phenobarbital; 1 CBZ+primidone), CBZ being administered 3 times a day. After steady-state serum level determination, the first step was to increase CBZ dosage until a better control of seizures was reached. Thereafter associated drugs were gradually withdrawn so that all patients were on CBZ monotherapy. At this point, when seizures became more numerous, the CBZ dose was increased until a total daily dosage of 30 mg/Kg was reached. Finally if complete control was not achieved notwithstanding the high CBZ dosage, phenytoin was added. During monotherapy, when a decrease of seizures was observed only for a brief period following CBZ dose increments, weekly sampling was performed in order to test for a possible relationship between weekly serum level variations of CBZ, its main metabolite CBZ-epoxide (CBZ-E), and the number of seizures. Blood samples were drawn before morning dose. Seizure frequency was recorded in diaries kept by relatives. CBZ and CBZ-E serum concentrations were determined in duplicate by HPLC [3]. Of the 6 patients studied 2 were controlled by CBZ monotherapy. The other 4 patients had limited benefit from an increase of CBZ doses but not complete control of seizures, which subsided only after administration of phenytoin. In these patients, after the first increment of CBZ dose during monotherapy, we observed an improvement lasting for about 2-3 weeks, after

High-pressure liquid chromatographic method for antipyrine kinetics in pediatric patients.

Summary A high-pressure liquid chromatographic (HPLC) method for the serum assay of antipyrine is described. 100 ul of serum are required for a single estimation. The method involves a chloroform extraction of the drug and carbamazepine (internal standard) from alkalinised serum. HPLC separation (Silica gel column, methanol-water as a mobile phase) lasts 3 min and enables about 60 samples to be assayed daily.

Phosphodiesterase activity of normal skeletal muscle of children.

Abstract Phosphodiesterase (PDE) activity of three preparations (homogenate, particulate and soluble fractions) of normal skeletal muscle of children aged 1–13 was studied. No significant differences in PDE activity were observed in respect to the age. The preparations showed similar properties to those from animal tissues. At least two different apparent km were demonstrated. Enzyme activity was sensitive to papaverine, theophylline and EGTA. Imidazole stimulated only the soluble preparation.