Pharmacodynamic Comparison of Two Formulations of Voglibose 0.3-mg Tablet

Mi Jo Kim; Hyeong-Seok Lim; Sang-Heon Cho; Kyun-Seop Bae

doi:10.12793/jkscpt.2013.21.1.34

Journal List > J Korean Soc Clin Pharmacol Ther > v.21(1) > 1055129

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Kim, Lim, Cho, and Bae: Pharmacodynamic Comparison of Two Formulations of Voglibose 0.3-mg Tablet

Original Article

J Korean Soc Clin Pharmacol Ther 2013;21(1):34-40.

Published online: 11 January 2013

DOI: https://doi.org/10.12793/jkscpt.2013.21.1.34

Pharmacodynamic Comparison of Two Formulations of Voglibose 0.3-mg Tablet

Mi Jo Kim^1,², Hyeong-Seok Lim^1,², Sang-Heon Cho³, Kyun-Seop Bae^1,²

¹Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Korea

²University of Ulsan College of Medicine

³Department of Clinical Pharmacology, Inha University Hospital, Inha University School of Medicine

E-mail: ksbae@amc.seoul.kr

Received 23 May 201324 June 2013 Accepted 26 June 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

Voglibose, an inhibitor of α-glucosidase of the small intestine brush border, is used to treat type 2 diabetic patients. Bioequivalence test based on pharmacokinetic parameters is difficult because voglibose does not cross the enterocytes after ingestion. This study was conducted to establish bioequivalence of two formulations of 0.3-mg voglibose with pharmacodynamic endpoints.

Methods:

This study was an open, single-dose, randomized, 6-sequence, 3-period crossover design in healthy volunteers. In each period, subjects received placebo or three tablets of either test formulation or reference formulation with sucrose, with a 7-day washout period each dosing period. Serial blood samples were collected after each administration. The maximum concentrations of serum glucose and serum insulin (C_max(G) and C_max(I)) and the area under the serum concentration - time curve from dosing to 2 or 4 hours after dosing for serum glucose and insulin (AUC_0-2h(G), AUC_0-4h(G), AUC_0-2h(I) and AUC_0-4h(I), respectively) were determined by noncompartmental analysis. Formulation-related differences were tested in accordance with the Korean regulatory bioequivalence criteria.

Results:

A total of 54 subjects completed study in accordance with protocol. The geometric mean ratios (GMRs) of the test formulation to the reference formulation for Cmax(G), AUC_0-2h(G), AUC_0-4h(G), C_max(I), AUC_0-2h(I) and AUC_0-4h(I) were 0.945, 1.014, 0.995, 0.937, 0.985 and 0.983, respectively and the 90 % confidence intervals (CIs) of corresponding values were 0.985-1.026, 0.991-1.038, 0.977-1.014, 0.830-1.057, 0.901-1.078 and 0.911-1.014, respectively.

Conclusion:

This single-dose study found that two formulations of 0.3-mg voglibose did not meet the regulatory criteria for bioequivalence in these healthy volunteers.

Keywords: Voglibose, Therapeutic equivalency, Pharmacodynamics

REFERENCES

1. Vichayanrat A, Ploybutr S, Tunlakit M, Watanakejorn P. Efficacy and safety of voglibose in comparison with acarbose in type 2 diabetic patients. Diabetes Res Clin Pr. 2002; 55(2):99–103.

2. Temelkova-Kurktschiev TS, Koehler C, Henkel E, Leonhardt W, Fuecker K, Hanefeld M. Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA(1c) level. Diabetes Care. 2000; 23(12):1830–1834.

3. Global Guideline for Type 2 Diabetes. International Diabetes Federation;2012.

4. Oak W. Bioavailability and Bioequivalence Studies for Orally Administered DrugProducts - General Considerations. US Food and Drug Administration;2003.

5. Draft Guidance on Acarbose. US Food and Drug Administration;2009.

6. Cramp DG. New automated method for measuring glucose by glucose oxidase. J Clin Path. 1967; 20:910–912.

7. Zhang M, Yang J, Tao L, Li L, Ma P, Fawcett JP. Acarbose bioequivalence: exploration of new pharmacodynamic parameters. AAPS J. 2012; 14(2):345–351.

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Figure 1.

Mean (S.E.) serum glucose concentration-time curve.

Figure 2.

Mean (S.E.) serum insulin concentration-time curve.

Table 1.

Treatment sequence by period

Sequence group	Number of subjects	Period 1	Period 2	Period 3
1	10	Placebo	Test	Reference
2	10	Placebo	Reference	Test
3	10	Test	Placebo	Reference
4	10	Test	Reference	Placebo
5	10	Reference	Placebo	Test
6	10	Reference	Test	Placebo

Table 2.

The demographic characteristics of randomized subjects

	Sequence						Total	P-value
	1(n=10)	2(n=10)	3(n=10)	4(n=10)	5(n=10)	6(n=10)	Total	P-value
Age(years)	26.7 (3.3)	25.9 (4.2)	24.3(2.0)	25.0(1.9)	23.7(1.5)	24.5(2.0)	25.1(2.8)	0.1782
Height(cm)	173.2(4.2)	175.1(5.4)	179.7(8.3)	171.4(3.5)	172.8(7.2)	176.0(8.1)	174.3(6.5)	0.1959
Weight(kg)	69.1(3.7)	71.8(8.9)	67.4(7.3)	68.4(7.3)	66.6(6.9)	68.8(7.0)	68.8(6.9)	0.6925

Values are presented as mean and standard deviation.

Table 3.

Pharmacodynamic parameters following a single oral administration of three tablets of 0.3-mg voglibose or placebo with sucrose in healthy Korean subjects (N=54)

Parameters	Placebo	Vogli	Basen
C_max(G)* (mg/dL)	144.22 ± 28.18	137.96 ± 17.26	140.56 ± 26.41
AUC_0-2h(G)^† (mg·hr/dL)	217.53 ± 24.45	209.05 ± 21.71	205.99 ± 3.55
AUC_0-4h(G)^‡ (mg·hr/dL)	384.55 ± 28.75	381.55 ± 26.04	383.52 ± 35.41
C_max(I)^§ (µIU/mL)	82.35 ± 41.05	75.52 ± 76.29	84.28 ± 48.88
AUC_0-2h(I)^¶ (µIU·hr/mL)	75.81 ± 34.94	61.29 ± 26.50	69.93 ± 30.12
AUC_0-4h(I)^¶ (µIU·hr/mL)	93.37 ± 38.47	78.75 ± 31.58	82.01 ± 34.61

* Maximum serum glucose concentration. ^†Area under the serum glucose versus time curve from dosing to 2 hours post-dose. ^‡ Area under the serum glucose versus time curve from dosing to 4 hours post-dose. ^§ Maximum serum insulin concentration. ¶ Area under the serum insulin versus time curve from dosing to 2 hours post-dose. ¶ Area under the serum insulin versus time curve from dosing to 4 hours post-dose.

Table 4.

Comparison of the geometric mean ratio (90 % confidence interval) of parameters for Basen or Vogli

Parameters	Geometric Mean
Parameters	Placebo	Vogli	Basen
C_max(G)* (mg/dL)	141.95	136.91	138.55	0.945(0.985-1.026)
AUC_0-2h(G)^† (mg·hr/dL)	215.66	207.57	204.23	1.014(0.991-1.038)
AUC_0-4h(G)^‡ (mg·hr/dL)	382.74	380.3	380.99	0.995(0.977-1.014)
C_max(I)^§ (µIU/mL)	73.38	72.24	66.47	0.937(0.830-1.057)
AUC_0-2h(I)^¶ (µIU·hr/mL)	66.81	54.11	56.02	0.985(0.901-1.078)
AUC_0-4h(I)^¶ (µIU·hr/mL)	84.13	71.08	73.45	0.983(0.911-1.014)

* Maximum serum glucose concentration. ^† Area under the serum glucose versus time curve from dosing to 2 hours post-dose. ^‡ Area under the serum glucose versus time curve from dosing to 4 hours post-dose. ^§ Maximum serum insulin concentration. ¶ Area under the serum insulin versus time curve from dosing to 2 hours post-dose. ¶ Area under the serum insulin versus time curve from dosing to 4 hours post-dose.

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