Urinary alkalisation for symptomatic uncomplicated urinary tract infection in women.

BACKGROUND: Uncomplicated urinary tract infection (UTI) is the most common bacterial infection in women, characterised by dysuria and urinary frequency. Urinary alkalisers are widely used in some countries for the symptomatic treatment of uncomplicated UTI, and they are recommended in some national formularies. However, there is a lack of empirical evidence to support their use for UTI and some healthcare guidelines advise against their use. OBJECTIVES: We aimed to look at the benefits and harms of the use of urinary alkalisers for the treatment of uncomplicated UTIs in adult women. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 19 January 2016 through contact with the Trials Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs on the use of (any) urinary alkalisers (either exclusively or non-exclusively) for the symptomatic treatment of uncomplicated UTI amongst women aged 16 and over, were included. Studies were eligible if they included patients whose diagnosis of UTI was decided by symptoms alone, or positive urine dipstick test or urine culture; and patients with recurrent UTI, provided patients had no symptoms of UTI in the two weeks prior to the onset of symptoms that lead them to seek medical advice. Studies were ineligible if they studied patients with complicated UTIs; immune-compromising conditions; acute pyelonephritis; or chronic conditions such as interstitial cystitis. DATA COLLECTION AND ANALYSIS: Three authors independently assessed and screened papers, and this was repeated by two separate authors (independently). An additional investigator acted as arbitrator, where necessary. There were no papers which fulfilled the inclusion criteria for this review, and therefore no data extraction was performed. MAIN RESULTS: Our search identified 172 potential studies for inclusion. However, following assessment none fulfilled the inclusion criteria for this review. AUTHORS' CONCLUSIONS: Until relevant evidence is generated from randomised trials, the safety and efficacy of urinary alkalisers for the symptomatic treatment of uncomplicated UTI remains unknown.

Predicted metabolic drug clearance with increasing adult age.

AIM: To determine the effect of increasing adult age on predicted metabolic drug clearance. METHOD: Predicted metabolic drug clearances (CLPT ) were determined using in vitro-in vivo extrapolation coupled with physiological-based pharmacokinetic modelling and simulation (IVIVE-PBPK) in Simcyp®. Simulations were conducted using CYP-selective 'probe' drugs with subjects in 5 year age groups (20-25 to 90-95 years). CLPT values were compared with human pharmacokinetic data stratified according to age (young = 20-40 years and elderly = 65-85 years) and gender. Age-related changes in the physiological parameters used for IVIVE of CLPT were described. RESULTS: Predicted metabolic drug clearances decreased with increasing adult age to approximately 65-70 years: caffeine from 1.5 to 1.0 ml min(-1) kg(-1) (a 33% decrease), S-warfarin from 0.100 to 0.064 ml min(-1) kg(-1) (36%), S-mephenytoin from 4.1 to 2.5 ml min(-1) kg(-1) (39%), desipramine from 10.6 to 7.3 ml min(-1) kg(-1) (31%) and midazolam from 5.4 to 3.9 ml min(-1) kg(-1) (27%). Except for S-mephenytoin, predictions were within 3.5-fold of clearances from clinical studies when stratified by age and gender. A trend towards higher CLPT was observed in females, but this was only statistically significant in larger virtual trials. Physiological parameters that determine CLPT decreased with increasing adult age: mean microsomal protein g(-1) of liver, liver weight, hepatic blood flow and human serum albumin concentration. CONCLUSION: Decreased metabolic clearance in the elderly was predicted by Simcyp® and was generally consistent with limited clinical data for four out of five drugs studied and the broader literature for drugs metabolized by CYP enzymes. IVIVE-PBPK may be increasingly useful in predicting metabolic drug clearance in the elderly.