First North American experience of propiverine use in children with overactive bladder

IntroductionIn 2017, propiverine was approved in Canada for overactive bladder (OAB) in adults and children. There is, however, scarce data on its efficacy and tolerability in the pediatric population. Our primary objective was to assess the efficacy and tolerability of propiverine as a treatment for pediatric OAB. Our secondary objective was to compare propiverine to molecules already investigated in historical cohorts.MethodsWe conducted a retrospective analysis of a prospectively maintained database and reviewed 58 patients who received propiverine since 2017. Efficacy and tolerability were assessed through voiding diaries, postvoid residuals (PVR), changes in the number of incontinence and urgency episodes (grade 1 to 3), and on reported adverse events.ResultsIn total, 58 patients (37 boys) initiated treatment at a mean age of 9.5±3.2 years. Patients were on propiverine for an average of 15.9±12.4 months. Mean bladder capacity increased from 120 ml to 216 ml, and % expected bladder capacity (%EBC) increased from 37% to 59%. The average increased rate of %EBC was 0.5% per month (p<0.001). Of the 58 patients, eight stopped the medication completely without symptom recurrence, 21 were still on medication, and six were on dose-tapering. Due to side effects, seven interrupted their treatment. Compared to molecules used in our service, propiverine offered comparable efficacy and tolerability. Our study had limitations, including the absence of a placebo group and its retrospective design.ConclusionsPropiverine appears to be an efficient and safe option for treating OAB in children and is approved as such.     

Assay of plasma isosorbide dinitrate and its metabolites after oral administration of immediate and delayed-action forms

This paper describes a kinetic comparative study of plasma concentrations of isosorbide dinitrate (ISDN) and its mononitrate derivatives (2-ISMN or 5-ISMN) after oral administration of a sustained release form of ISDN or a (non) sustained release form of 5-ISMN. The blood extracts determinations were performed by electron capture gas chromatography which is an accurate and sensitive method suitable for the quantitation of concentrations in the nanogram per ml range. The results are in good agreement with those of the literature. The standard form of 5-ISMN is rapidly absorbed. The Tmax value is approximately 1H with a corresponding Cmax value close to 400 ng/ml. For the sustained release drugs, the Tmax increases to 6H and Cmax is nearly half the 5-ISMN standard form value. Considering the administered dose, it seems better to use 5-ISMN than ISDN. For a long lasting treatment of angina pectoris and ischaemic cardiac diseases, both forms can be used.     

5-Fluoro (3H) pyrimidine-4-ones: synthesis, reactivity and pharmacological properties]

Fourteen fluoro pyrimidine-4-ones, four fluoro bispyrimidine-4-ones and two fluoro pyrimidine-4-ones with fused ring have been prepared. The reactivity of the carbonyl group of two pyrimidine-4-ones phosphorus oxychloride was studied. The 4-chloro pyrimidines reacted with ammonia or morpholine giving 4-substituted pyrimidines. Eight compounds are evaluated for their anti-inflammatory and anti-convulsivant properties: they were found to be weakly active against oedema and three of them protected rats form tonic convulsions.     

Systemic and regional hemodynamic interactions of perindopril and nitrendipine in the spontaneously hypertensive rat.

Adult spontaneously hypertensive rats (SHR) were daily treated for 2 weeks with perindopril [an angiotensin-converting enzyme (ACE) inhibitor] and nitrendipine (a calcium antagonist) alone or in combination. Blood pressure (BP), heart rate (HR), and diuresis were assessed weekly in conscious rats, and systemic and regional hemodynamics were investigated by the microsphere technique at the end of the treatment in anesthetized rats. Both perindopril (2 mg.kg-1.d-1) and nitrendipine (10 mg.kg-1.d-1) decreased BP to the same extent, but perindopril exerted a longer action. The hemodynamic profile of each drug was respectively consistent with the classic ones of ACE inhibitors and calcium antagonists already described in the literature. With combination of the two treatments, effects were at least additive, except that the nitrendipine-induced tachycardia was partially reduced by perindopril. BP reduction was additive, and significant potentiation was shown at the systemic [cardiac index (CI) increase, total peripheral resistance (TPR) decrease] and some regional (hepatic, muscular, and cutaneous vasodilations) levels. These results, which are in agreement with the different mechanisms of action of the two drugs, emphasize the advantage of combining perindopril with nitrendipine for treatment of hypertension.     

A cohort study of Plasmodium falciparum diversity during the dry season in Ndiop, a Senegalese village with seasonal, mesoendemic malaria

Prolonged carriage of Plasmodium falciparum in humans during the dry season is critical for parasite survival, as the infected subjects constitute a major reservoir in the absence of transmission. Yet, very little is known about the host/parasite interactions contributing to parasite persistence. In order to study the characteristics of P. falciparum infections during the dry season, we have genotyped parasites collected from untreated, asymptomatic individuals during 3 cross-sectional surveys conducted during the dry season in Ndiop, a Senegalese village with seasonal, mesoendemic malaria. Monthly entomological surveillance did not detect any transmission during that period. Parasite prevalence decreased markedly in the children aged < 7 years after 7 months of undetected transmission, but was stable in older children and adults throughout the dry season. In all chronically infected individuals, infection complexity remained stable, but there were substantial fluctuations of individual genotype(s), reflecting complex dynamics of multiple-clone infections during chronic asymptomatic parasite carriage. This fluctuation resulted in changes in the msp1 and msp2 allelic distribution within the cohort after 7 months of undetected transmission, contrasting with the stability observed during the preceding rainy season in that village.