RESUMO
Background: Sodium bicarbonate supplementation is a mainstay in the treatment of metabolic acidosis in patients with chronic kidney disease (CKD). Recent studies showed reduction of progression of CKD and reduced all-cause mortality. However, additional sodium loading could worsen arterial hypertension, a well-known contributor to progression of CKD. This patient-relevant and economically negative side effect is under-studied in prospective studies up until now. Objective: The aim of this study was to analyze the effect of sodium bicarbonate treatment on arterial blood pressure at baseline and after 8 weeks. Methods: The SoBic study is an ongoing randomized controlled trial, in which patients with CKD receive either a high dose of oral sodium bicarbonate or a rescue treatment, if necessary. We used standardized office blood pressure and 24-hour ambulatory blood pressure monitoring (24h-ABPM). Regression models were adjusted for estimated glomerular filtration rate and change of antihypertensives. Results: 47 subjects were enrolled and the mean age was 57 (±14.6) years and 18 (38%) were female. In 43 randomized subjects with sufficiently performed 24h-ABPM neither systolic 24h-ABPM (2.522; 95%CI: -2.364, 7.408; mmHg) nor diastolic 24h-ABPM (0.868; 95%CI: -2.411, 4.147; mmHg) was affected by study group allocation. When looking at the effect of individual sodium bicarbonate dose on 24h-ABPM, the fully adjusted model suggested an increase of 0.047 (95%CI: -0.026, 0.119) mmHg by each mg/kg per day increase of sodium bicarbonate dose. Conclusion: Sodium bicarbonate supplementation over 8 weeks did not significantly increase blood pressure measured by 24h-ABPM in CKD patients. Trial Registration: EUDRACT Number: 2012-001824-36; 12/07/2012 (https://www.clinicaltrialsregister.eu).
RESUMO
OBJECTIVES: The efficacy of an anti-infective drug is influenced by its protein binding (PB), since only the free fraction is active. We hypothesized that PB may vary in vitro and in vivo, and used clindamycin, a drug with high and concentration-dependent PB to investigate this hypothesis. METHODS: Six healthy volunteers received a single intravenous infusion of clindamycin 900 mg. Antibiotic plasma concentrations were obtained by blood sampling and unbound drug concentrations were determined by means of in vivo intravascular microdialysis (MD) or in vitro ultrafiltration (UF) for up to 8 h post dosing. Clindamycin was assayed in plasma and MD fluid using a validated HPLC-UV (ultraviolet) method. Non-linear mixed effects modelling in NONMEM® was used to quantify the PB in vivo and in vitro. RESULTS: C max was 14.95, 3.39 and 2.32 mg/L and AUC0-8h was 41.78, 5.80 and 6.14 mg·h/L for plasma, ultrafiltrate and microdialysate, respectively. Calculated ratio of AUCunbound/AUCtotal showed values of 13.9%±1.8% and 14.7%±3.1% for UF and microdialysate, respectively. Modelling confirmed non-linear, saturable PB for clindamycin with slightly different median (95% CI) dissociation constants (Kd) for the alpha-1 acid glycoprotein (AAG)-clindamycin complex of 1.16 mg/L (0.91-1.37) in vitro versus 0.85 mg/L (0.58-1.01) in vivo. Moreover, the estimated number of binding sites per AAG molecule was 2.07 (1.79-2.25) in vitro versus 1.66 in vivo (1.41-1.79). CONCLUSIONS: Concentration-dependent PB was observed for both investigated methods with slightly lower levels of unbound drug fractions in vitro as compared with in vivo.
Assuntos
Antibacterianos , Clindamicina , Voluntários Saudáveis , Humanos , Microdiálise , Ligação ProteicaRESUMO
To evaluate the incidence of endometriosis in polycystic ovary syndrome (PCOS) patients who did not present with any endometriosis symptoms and underwent laparoscopic ovarian drilling (LOD) for clomiphene citrate (CC) resistance, 225 and 630 women with CC-resistant PCOS without classic endometriosis symptoms were included in a retrospective study and a meta-analysis, respectively. All women underwent LOD. The main outcome parameter was the prevalence of incidental endometriosis. Laparoscopy revealed endometriosis in 38/225 (16.9%) women (revised American Fertility Society (rAFS) stage I: 33/38, 86.8%; rAFS stage II: 5/38, 13.2%). When women with CC-resistant PCOS without endometriosis were compared, lower body mass index (BMI) and lower 25-hydroxy-vitamin D levels were associated with the presence of endometriosis at laparoscopy (odds ratios (OR): 0.872, 95% confidence intervals (95%CI): 0.792-0.960; p = 0.005 and OR: 0.980, 95%CI: 0.962-0.999; p = 0.036; respectively). The inclusion criteria for the meta-analysis were fulfilled by 4/230 reports about LOD. After correction for study heterogeneity, the pooled prevalence of incidental endometriosis was 7.7% in women with CC-resistant PCOS. In conclusion, the rate of incidental endometriosis in women with CC-resistant PCOS might reflect the prevalence of asymptomatic endometriosis. All cases were affected by minimal or mild disease. Since the literature lacks reports on associated clinical outcomes, the relevance of this entity in such patients should be the subject of further studies.