Pharmacological Research 49 (2004) 93–98 Bioequivalence assessment of ambroxol tablet after a single oral dose administration to healthy male volunteers Hee Joo Lee a,b,∗ , Sun Koung Joung b , Yoon Gyoon Kim c , Jeong-Yeon Yoo b , Sang Beom Han a,b a Department of Pharmacokinetics, Seoul Medical Science Institutes, 7-14, Dongbinggo-Dong, Yongsan-Gu, Seoul 140-809, South Korea b Department of Pharmacokinetics, BioCore Co., Ltd., Heasan Bldg. 108-1, Yangjea-Dong, Seocho-Gu, Seoul 137-130, South Korea c Department of Pharmacology, College of Medicine, Dankook University, San 29, Anseo-Dong, Chonan-Si, Choungnam 330-714, South Korea Accepted 30 July 2003 Abstract A bioequivalence study of the ambroxol hydrochloride tablets was conducted. Twenty-four healthy male Korean volunteers received each medicine at the ambroxol hydrochloride dose of 30 mg in a 2 × 2 cross-over study. There was a 1-week washout period between the doses. Plasma concentrations of ambroxol were monitored by a high-performance liquid chromatography (HPLC) for over a period of 24 h after the administration. AUC t (the area under the plasma concentration–time curve from time 0 to last sampling time, 24 h) was calculated by the linear-log trapezoidal rule method. C max (maximum plasma drug concentration) and T max (time to reach C max ) were compiled from the plasma concentration–time data. Analysis of variance was carried out using logarithmically transformed AUC t and C max , and untransformed T max . The geometric mean of AUC t was 495.8 ng ml -1 h -1 (test medication) and 468.3 ng ml -1 h -1 (reference medication). C max of 61.5 and 57.3 ng ml -1 were achieved for the test and the reference medication, respectively. The point estimates and 90% confidence intervals for AUC t (parametric) and C max (parametric) were, in point estimate (90% confidence interval), 1.058 (0.989–1.134) and 1.073 (1.007–1.142), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value of T max was 0.229 (0.015–0.444). These results indicate that the two medications of ambroxol hydrochloride are bioequivalent and, thus, may be prescribed interchangeably. © 2003 Elsevier Ltd. All rights reserved. Keywords: Bioequivalence study; Ambroxol; Volunteers; Pharmacokinetics 1. Introduction Ambroxol (trans-4-(2-amino-3,5-dibromobenzyl)-amino- cyclo-hexanol) is an active metabolite of bromhexin and has been used to increase surfactant secretion in the lungs. Am- broxol has also been reported to have a cough-suppressing effect [1] and anti-inflammatory action [2]. Recently, the in- hibition of nitric oxide (NO)-dependent activation of solu- ble guanylate cyclase was suggested one of the molecular mechanism of the therapeutic action of ambroxol [3]. It is frequently used in the treatment of bronchial asthma and chronic bronchitis [4], and also used in pulmonary alveolar proteinosis and infant respiratory distress syndrome [5]. In spite of its frequent use, reports for pharmacokinetic properties of ambroxol are limited [6–9]. After single oral ∗ Corresponding author. Tel.: +82-2-3461-0542; fax: +82-2-3461-0590. E-mail address: hjlee@bio-core.com (H.J. Lee). administration of 30 mg ambroxol tablet to 12 healthy vol- unteers, C max and T max were 56 ± 25 ng ml -1 and 2 h, re- spectively, and absolute bioavailability was 72.9 ± 39.4 [8]. After single oral administration of ambroxol 75 mg sustained release capsule to 12 healthy volunteers, terminal half-life was about 10.5 h and C max and T max were 97 ± 29 ng ml -1 and 4.2 ± 1.1 h, respectively [9]. Since Shin Poong Pharm. Co., Ltd. (Seoul, Korea) produced new formulation of ambroxol hydrochloride, the bioequivalence assessment of the two formulations, Roisol tablets (test medication) and Mucopect tablet (ref- erence medication, manufactured by Boehringer Ingelheim Korea, Seoul, Korea) was assessed in 24 healthy male Korean volunteers in this study. Typical bioavailability parameters, such as AUC t (the area under the plasma concentration–time curve from 0 to last sampling time), C max (the maximum plasma concentration), and T max (the time to reach C max ) of ambroxol were obtained and compared. 1043-6618/$ – see front matter © 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.phrs.2003.07.011