ABSTRACT
Purpose
Hypertension is often observed in patients with diabetes, and the progression of diabetic
nephropathy is closely related to blood pressure elevation. Thus, the effects of hypoglycemic
drugs on kidney function and pharmacokinetic interactions in combination with antihypertensive
and hypoglycemic drugs are of great clinical value. The purpose of this study was
to evaluate the pharmacokinetic interactions between henagliflozin (SHR3824), a new
sodium-dependent glucose transporter 2 (SGLT2) inhibitor class drug, and valsartan,
an angiotensin II receptor blocker.
Methods
A single-center, single-arm, open-label, self-controlled study was conducted in healthy
Chinese volunteers. The pharmacokinetic parameters were calculated with Phoenix WinNonlin
version 7.0, and the statistical analysis was performed with SAS version 9.4. Data
on pharmacokinetic parameters (single and/or steady-state) were collected and tabulated
for different analytes (valsartan and SHR3824) according to the sampling time specified
in the protocol. Continuous attention was paid to the safety of all subjects. The
aim of the study was to evaluate the effect of a single dose of valsartan on the pharmacokinetic
behavior of SHR3824 after multiple doses of SHR3824 (Cmax,ss and AUCτ,ss) and the effect of multiple doses of SHR3824 on the pharmacokinetic behavior of valsartan
(Cmax, AUC0–24h, and AUC0–∞). A mixed effect model was used to estimate the point estimation and 90% CI of the
geometric mean ratio of the corresponding pharmacokinetic indices at the combined-medication
stage (SHR3824 + valsartan) and the single-medication stage (SHR3824 or valsartan).
Findings
Twelve volunteers were screened into this experiment and underwent blood sampling.
The pharmacokinetic properties of SHR3824 were evaluated after its administration
alone or in combination with valsartan. Point estimates and 90% CIs of the geometric
mean ratio of SHR3824 Cmax,ss and AUCτ,ss were within the conventional bioequivalence range of 80% to 125%. The pharmacokinetic
properties of valsartan were evaluated after its administration alone or in combination
with SHR3824. The geometric mean ratios and 90% CIs of the valsartan Cmax, AUC0–24h, and AUC0–∞ were also within the range of 80% to 125%. Thirty-four mild adverse events were reported,
with no serious adverse events or suspected unexpected serious adverse reactions.
Implications
This study provides basis for the clinical co-administration of SHR3824 with angiotensin
II receptor blockers represented by valsartan. Based on these findings, co-administration
of SHR3824 and valsartan seemed to have no effect on the pharmacokinetic properties
of either drug. Chinadrugtrials.org.cn Identifier: CTR20180002.
Keywords
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Article info
Publication history
Published online: June 28, 2022
Accepted:
June 3,
2022
Identification
Copyright
© 2022 Elsevier Inc.
