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As with any other study method, 'spontaneous reporting' in pharmacovigilance is a process of data acquisition, assessment, presentation and interpretation. The provision of information (i.e. of interpreted data) concerning previously unknown, or otherwise important adverse drug reactions is a major goal. The assessment of case reports in spontaneous reporting takes place in 2 steps: first the assessment of each case individually, and secondly the interpretation of the aggregated data. The latter step is only completed for a minority of case reports, such as when actions or measures are deemed necessary. Uncertainty in case reports regarding the involvement of the suspected drugs is an inherent drawback of spontaneous reporting. Standardised case-causality assessment has become a routine at pharmacovigilance centres around the world. It aims at a decrease in ambiguity of the data and plays a role in data exchange and the prevention of erroneous conclusions. A variety of systems for standardised causality assessment have been developed, ranging from short questionnaires to comprehensive algorithms. Since none of the available assessment systems has been validated (i.e. shown to consistently and reproducibly produce a fair approximation of the truth), causality assessment has only limited scientific value. Causality assessment neither eliminates nor quantifies uncertainty but, at best, categorises it in a semiquantitative way. Routine causality assessment is usually part of the first step in case assessment, and is based on a general system that is intended for all reactions and all drugs. During the subsequent phase of aggregated assessment, causality assessment is likely to be repeated and the use of a specific aetiological-diagnostic system may be more appropriate. It may be recommended to restrict case-causality assessment to selected case reports that are likely to play an active role in pharmacovigilance and to use specific systems, adapted to the reaction or problem involved. It is an inherent limitation of spontaneous reporting that, with the exception of rare proof-positive case reports, conclusive evidence cannot usually be produced. Standardised causality assessment has not really changed this situation. As a rule, confirmation of the connection between a drug and an adverse reaction requires further analytical or experimental study.

In this review we summarized literature data on the mechanisms of human placental drug transport studied in the isolated perfused placental cotyledon, placental membrane vesicles or trophoblastic cell cultures. Overall human placental drug transport rarely exceeds the transfer of flow-dependent and membrane-limited marker compounds. Interestingly, relatively often placental drug transfer appeared to be much smaller, indicating impaired trans-placental transport, depending on the physico-chemical characteristics of the drug or placental factors such as tissue binding or metabolism. Although in perfusion studies overall human placental drug transport occurs by simple diffusion, at the membrane level several drug transport systems have been found, mainly for drugs structurally related to endogenous compounds.

Influence of non-steroidal anti-inflammatory drugs on diuretic treatment of mild to moderate essential hypertension P P KOOPMANS, TH THIEN, F W J GRIBNAU AbstractIn an open triple crossover study in 10 patients with mild to moderate essential hypertension the influence was investigated of adding indomethacin 50 mg, naproxen 250 mg, or sulindac 200 mg, each twice daily for four weeks, to diuretic treatment with hydrochlorothiazide 50 mg a day.After two weeks' treatment with indomethacin a slight increase in blood pressure was observed, whereas both sulindac and naproxen tended to enhance the antihypertensive effect of hydrochlorothiazide. After treatment for four weeks, however, the effects of all three drugs on blood pressure appeared to be blunted. Furthermore, body weight increased significantly during treatment with indomethacin but not during treatment with naproxen or sulindac. No significant changes were found for various biochemical variables, including concentrations of plasma electrolytes and serum creatinine and albumin, plasma renin activity, plasma aldosterone concentration, and 24 hour urinary excretion of sodium and potassium, with the exception, however, of an increase in plasma potassium concentration during treatment with indomethacin.These observations suggest that the interaction of indomethacin, naproxen, and sulindac with diuretic treatment in mild to moderate essential hypertension is transient and of minor clinical importance.

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