Results: Thirty participants were enrolled (16 men,
14 women; all white; mean age, 43.7 years). Canagli-
flozin AUC during a dosing interval (T) at steady state
(AUCτ,ss) and Cmax at steady state (Cmax,ss) were
increased when canagliflozin was coadministered with
HCTZ, with geometric mean ratios (90% CI) of 1.12
(1.08–1.17) and 1.15 (1.06–1.25), respectively. AUCτ,ss
and Cmax,ss for HCTZ were similar with and without
canagliflozin coadministration. The 24-hour mean renal
threshold for glucose and mean plasma glucose
were comparable for canagliflozin alone and coadministered
with HCTZ. The change in 24-hour urine
volume from baseline was 0.1 L with canagliflozin
alone and 0.4 L with HCTZ alone and with canagli-
flozin þ HCTZ. The overall incidence of adverse events
(AEs) was higher with canagliflozin þ HCTZ (69%)
than with canagliflozin (47%) or HCTZ (50%) alone;
most AEs were of mild severity. Overall, minimal
changes in serum electrolytes (eg, sodium, potassium)
were observed after coadministration of canagliflozin þ
HCTZ compared with individual treatments.
Results: Thirty participants were enrolled (16 men,14 women; all white; mean age, 43.7 years). Canagli-flozin AUC during a dosing interval (T) at steady state(AUCτ,ss) and Cmax at steady state (Cmax,ss) wereincreased when canagliflozin was coadministered withHCTZ, with geometric mean ratios (90% CI) of 1.12(1.08–1.17) and 1.15 (1.06–1.25), respectively. AUCτ,ssand Cmax,ss for HCTZ were similar with and withoutcanagliflozin coadministration. The 24-hour mean renalthreshold for glucose and mean plasma glucosewere comparable for canagliflozin alone and coadministeredwith HCTZ. The change in 24-hour urinevolume from baseline was 0.1 L with canagliflozinalone and 0.4 L with HCTZ alone and with canagli-flozin þ HCTZ. The overall incidence of adverse events(AEs) was higher with canagliflozin þ HCTZ (69%)than with canagliflozin (47%) or HCTZ (50%) alone;most AEs were of mild severity. Overall, minimalchanges in serum electrolytes (eg, sodium, potassium)were observed after coadministration of canagliflozin þHCTZ compared with individual treatments.
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