ABSTRACT
PURPOSE: Dose modification in renal impairment has traditionally been based on changes in estimated glomerular filtration rate (eGFR; estimated by creatinine clearance). However, many drugs are eliminated by tubular anionic and cationic transport where changes in eGFR may not necessarily reflect changes in tubular function. This study investigated the relationship between GFR and renal tubular function with reference to drug handling by using accepted drug probes. METHODS: Three drug probes, (51)Cr-EDTA, fluconazole, and pindolol, were administered to patients who had varying degrees of renal impairment. Blood sampling, assays, and a pharmacokinetic analysis were performed for all drug probes and endogenous urate. Measured GFR ((51)Cr-EDTA clearance; mGFR) was compared to tubular anionic transport (urate clearance), tubular reabsorption (fluconazole clearance), and tubular cationic transport (S-pindolol clearance). RESULTS: A moderately strong association was demonstrated between the measured isotopic GFR and creatinine clearance (R(2) = 0.78). A moderate positive correlation was found between mGFR and proximal tubular anion transport and reabsorption (R(2) = 0.40-0.44, p < 0.0001). In contrast, cationic secretion correlated poorly with mGFR (R(2) = 0.11, p = 0.036). CONCLUSIONS: Given that drug dosing schedules utilise eGFR values as the basis for modifying drug dosing, our results would suggest that a recommendation of a dose reduction according to eGFR alone should be treated with caution.
Subject(s)
Glomerular Filtration Rate , Kidney Tubules, Proximal/metabolism , Renal Insufficiency/physiopathology , Adult , Aged , Aged, 80 and over , Biological Transport/physiology , Dose-Response Relationship, Drug , Edetic Acid/pharmacokinetics , Female , Fluconazole/pharmacokinetics , Humans , Kidney Function Tests/methods , Male , Middle Aged , Pindolol/pharmacokineticsABSTRACT
The effect of clinical priority access criteria for access to infertility treatment was examined for women outside the body mass index (BMI) range of 18-32 kg/m2. Treatments and outcomes were analysed from 1280 cases referred from 1998 to May 2005. Sixteen percent of women had a BMI of >32 kg/m2. Overall, 38% of these women had a birth from conceiving a treatment-related pregnancy or spontaneous pregnancy, compared with 52% of women with BMI < 32 kg/m2. Weight loss allowed women in the BMI group >32<35 kg/m2 to access treatment, but women in higher BMI groups were less successful.
