Relative bioavailability of diazoxide, manufactured at two different international locations, in healthy participants under fasting conditions: an open-label, two-stage, adaptive, sequential two-period crossover study

AAPS Open

Table 2 Pharmacokinetic results based on measured plasma study drug concentrations (N = 36)^a

Parameter	Product	GM	GM, 95% CI	GMR (Test vs Reference), %	GMR, 90% CI	Pseudo Intra-participant % CV^b
AUC_0-t, ng.hour/mL	Test	200,000	184,000–217,000	108.01	105.08-111.03	6.9
	Reference	185,000	170,000–201,000	-	-	-
AUC_0-inf, ng.hour/mL	Test	244,000	219,000–272,000	106.12	102.62–109.75	8.4
	Reference	230,000	206,000–257,000	-	-	-
C_max, ng/mL	Test	5,830	5,450–6,230	116.89	113.66–120.22	7.0
	Reference	4,990	4,680–5,320	-	-	-

AUC _0-inf area under the curve from time zero to infinity, AUC _0-t area under the curve from time zero to the time of the last measurable analyte concentration, C _max maximum plasma analyte concentration, CI confidence interval, CV coefficient of variation, GM geometric mean, GMR geometric mean ratio
^aA nonzero predose concentration level was obtained at the beginning of period 2 in one participant. However, the measured predose level was < 1% of the participant’s corresponding C_max value. In compliance with the protocol, the predose level was maintained in the pharmacokinetic analysis without baseline correction
^bEstimated based on the elements of the variance-covariance matrix as: CV(%) = 100*sqrt[(σA² + σB² − 2*σAB)/2], where A and B are the two treatments
Test, PROGLICEM® 100 mg hard capsules, Batch No.: 3107A (Merck Sharp & Dohme Corp, USA); reference, PROGLYCEM® 100 mg capsules, Lot No.: 120118 (Merck Canada Inc., Canada)