Pharmacokinetics of clomipramine during pregnancy.

PURPOSE: Clomipramine is one of the drugs for depression during pregnancy; however, pharmacokinetic data of clomipramine and its active metabolite desmethylclomipramine in this vulnerable period are lacking. In this study, we describe clomipramine and desmethylclomipramine concentrations including their ratios during pregnancy. Second, we describe Center for Epidemiologic Studies Depression scale (CES-D) scores during pregnancy. METHODS: During 13 pregnancies, every trimester and 3 months after pregnancy, the clomipramine and desmethylclomipramine concentrations were measured with LC-MSMS and the severity of depression was assessed by taking the CES-D score. All concentrations used in our calculations were in fact the ratio between actual plasma concentration (µg/l) and the actual dose (mg). We compared differences in ratios between trimesters by using the Friedman test. RESULTS: Studying 12 women and 13 pregnancies, we found no changes in mean clomipramine concentrations, a statistically significant decrease in mean desmethylclomipramine concentrations (p = 0.014) and a significant decrease in the ratio of desmethylclomipramine/clomipramine mean concentrations during pregnancy (p = 0.014) compared to the post-partum period. Sub-therapeutic concentrations of clomipramine and desmethylclomipramine were found in three patients during whole pregnancy. CONCLUSIONS: The mean concentrations of the pharmacologically active metabolite of clomipramine and desmethylclomipramine changes during pregnancy, where a decrease in mean concentrations was found during pregnancy. In case of recurrent disease, we recommend to control clomipramine and its metabolite concentrations, while both are active.

Concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine during pregnancy.

WHAT IS KNOWN AND OBJECTIVE: Depression during pregnancy is common and includes risks for mother and child. Pharmacokinetics of venlafaxine may be changed during pregnancy. This study aimed to describe changes in metabolic ratios and concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine during and after pregnancy. METHODS: To study this, we used data from our study of compliance to Antidepressants During Pregnancy (the ADAP study) to investigate the course of venlafaxine and O-desmethylvenlafaxine concentrations during pregnancy and in the period post-partum. RESULTS AND DISCUSSION: We found that the venlafaxine concentration significantly changed during pregnancy when compared to the post-partum period (P = 0·028). The median concentration of venlafaxine in the first trimester was 98·9% (54·2-292·0%), the second 100·0% (46·5-264·0%) and the third trimester 87·0% (61·5-217·2%). We did not found differences in O-desmethylvenlafaxine concentrations in the different trimesters of pregnancy compared with the post-partum period, P = 0·565. Also the ratio of O-desmethylvenlafaxine/venlafaxine concentrations increased significantly from 76·9% (range 32·8-142·0%) in the first trimester to 196·7% (range 83·3-427·6%) in the third trimester compared with the post-partum period, P = 0·004. Further, three of seven patients had concentrations below the therapeutic reference range (100-400 µg/L) in any period of pregnancy, whereas no one had subtherapeutic concentrations in the post-partum period. WHAT IS NEW AND CONCLUSION: Venlafaxine concentrations decreases during pregnancy, and the ratio of the concentrations of O-desmethylvenlafaxine/venlafaxine increases during pregnancy. Pregnant women using venlafaxine are at risk for subtherapeutic concentrations, therefore routine monitoring of concentrations venlafaxine and O-desmethylvenlafaxine is recommendable during pregnancy.

[Antidepressants during pregnancy and lactation]. / Antidepressiva tijdens zwangerschap en borstvoeding.

BACKGROUND: It is difficult to find well-grounded advice about the pharmacotherapeutic treatment of anxiety and depression before, during and after pregnancy. Furthermore, in the literature pharmacotherapeutic advice relating to the various periods (pre-conception, pregnancy and lactation) is often contradictory. AIM: By reviewing the literature, to arrive at a recommendation for the pharmacotherapeutic treatment of depression during and after pregnancy and to compare and weigh up the various risks involved in treatment. METHOD: A literature search in PubMed and Embase with search terms 'antidepress*', 'anxiol*', 'pregnan*', 'depressi*', 'anxiet*', 'guideline', 'lactation', 'breastfeeding' and 'milk'. The National Guideline Clearinghouse database was used to find guidelines. results The literature reveals that the medical treatment of a depression during pregnancy and lactation is not without risks. However, there are also risks involved in not treating depression during these periods. These risks cannot be assessed at group-level but have to be weighed up for each individual separately. The patient needs to be informed about the risks she runs in connection with a particular treatment so that a well-considered decision can be made about whether to treat or not treat depression with antidepressants during pregnancy. CONCLUSION: If the decision is made to treat depression during pregnancy and in the lactation period, it is advisable to choose an antidepressant from the safest category; in most countries this means opting for tricyclic antidepressants.

Endoneural selective stimulating using wire-microelectrode arrays.

In acute experiments eight 5- to 24-wire-microelectrode arrays were inserted into the common peroneal nerve of the rat, to investigate whether the electrodes could selectively stimulate motor units of the extensor digitorum longus (EDL) muscle. Twitch-force-recruitment curves were measured from the EDL for each array electrode. The curves were plotted on a double-logarithmic scale and parameterized by the low-force slope (which represents the power p in the power-law relationship of force F versus stimulus current I, or F approximately I(p)) and the threshold current. The slopes and threshold currents measured with array electrodes did not differ significantly from those obtained with randomly inserted single wire-microelectrodes. This indicates that, although involving a more invasive insertion procedure, electrode arrays provide neural contacts with low-force recruitment properties similar to those of single wires. Array results revealed partial blocking of neural conduction, similar to that reported with microneurographic insertion with single needles. The efficiency of the array was defined as the fraction of array electrodes selectively contacting a motor unit and evoking the corresponding threshold force. Efficiency thus expresses the practical value of the used electrode array in terms of the total number of distinct threshold forces that can be stimulated by selecting the appropriate electrodes. The eight arrays were capable of evoking threshold forces selectively with an average efficiency of 0.81 (or 81%).

Force-current relationships in intraneural stimulation: role of extraneural medium and motor fibre clustering.

Animal experiments and model simulations of monopolar, intrafascicular nerve stimulation are presented to study force-current relationships (recruitment curves). The conductivity of the extraneural medium is of prime importance to the resulting recruitment cures: an insulating extraneural medium generally leads to steeper curves with lower threshold currents than a well-conducting extraneural medium. Extensive statistical comparison of experimental and model results suggests the occurrence of clustering of alpha-motoneurons within the fascicle, manifesting itself mainly by an increased spread in threshold currents, as opposed to the situation where the fibres are distributed uniformly throughout the entire fascicle.

3D neuro-electronic interface devices for neuromuscular control: design studies and realisation steps.

In order to design the shape and dimensions of new 3D multi-microelectrode information transducers properly, i.e. adapted to the scale of information delivery to and from peripheral nerve fibres, a number of studies were, and still are, being performed on modelling and simulation of electrical volume conduction inside and outside nerves, on animal experiments on stimulation and recording with single wires and linear arrays, and on new technologies for 3D micro-fabrication. This paper presents a selection of the results of these "Neurotechnology' studies at the University of Twente. The experimental and simulation results apply primarily to the peripheral motor nerves of the rat, but are also of interest for neural interfacing with myelinated nerves in man, as fascicles in man are about the same size as in the rat.

Vitamin A deficiency in the captive African lion cub Panthera loe (Linnaeus, 1758).

Dietary, breeding and clinical histories and pathological findings are presented from 2 confirmed and 5 presumed cases of vitamin A deficiency in immature African lions. Five of the 7 animals were born in the wild while 2 were born in captivity. All animals were fed lean red meat sprinkled with a vitamin/mineral supplement. Salient clinical signs were incoordination, "star gazing", blindness and intermittent convulsions. Pathological lesions seen in 4 animals included severe thickening of the cranial bones, with consequent marked compression of the brain and partial herniation of the cerebellum. Vascular damage in the cerebellum and ensuing haemorrhages, resulting in acute increases of an already high intracranial pressure, were thought to be the cause of some of the clinical signs, particularly convulsions rather than direct pressure-necrosis and atrophy of nervous tissue.

Helminths recovered from the bontbok, Damaliscus dorcas dorcas (Pallas, 1776).

A report is given on the helminths collected from 4 bontbok, Damaliscus dorcas dorcas, which died following capture at the Bontebok National Park, Swellendam, and transfer to the National Zoological Gardens, Pretoria. Seven of these helminths are new host records. Lungworms submitted to the institute for identification over the last 2 years are also reported; these were all Dictyocaulus magna. The various scientific and common names that have been applied to the bontbok in the past are reviewed.