OBJECTIVE: To examine whether or not the early dissolution/absorption in the oral cavity of lozenge administration contributes to superior bioavailability of ambroxol compared with the commercially available tablet. METHODS: 24-hour plasma level pharmacokinetic profiles of 20 healthy volunteers receiving oral administration of identical single doses (30mg) of lozenges and a commercially available tablet with a 1-week washout period were collected. The data were analysed by a non-compartmental model with a statistical moment and mean transit time concept. The mean transit times obtained after lozenge and tablet administration were compared. RESULTS: The variance in absorption phase was significantly higher than that in the distribution/elimination phase in the pharmacokinetic profiles of the lozenge, suggesting additional absorption processes. The mean transit time of the tablet was significantly greater than that of the lozenge, by 7.69 hours with a 90% confidence interval (CI) of 3.11, 12.27. Early drug dissolution/absorption in the oral cavity and gastrointestinal absorption was successfully modelled to the pharmacokinetic profiles after lozenge administration. The additional availability of the drug to systemic circulation was mainly due to complete dissolution in the oral cavity prior to absorption as well as to oral mucosal transport. Between the two processes, dissolution was proposed to be a limiting step, since oral mucosal absorption was at a very high rate. The estimated average dissolution rate constant (90% CI) in first-order fashion was 0.13h(-1) (0.08, 0.32). CONCLUSION: Absorption rates between lozenge and tablet could be differentiated with the aid of the mean transit time concept. However, estimation of oral mucosal absorption was not possible because the blood sampling intervals were not sufficiently frequent.
OBJECTIVE: To examine whether or not the early dissolution/absorption in the oral cavity of lozenge administration contributes to superior bioavailability of ambroxol compared with the commercially available tablet. METHODS: 24-hour plasma level pharmacokinetic profiles of 20 healthy volunteers receiving oral administration of identical single doses (30mg) of lozenges and a commercially available tablet with a 1-week washout period were collected. The data were analysed by a non-compartmental model with a statistical moment and mean transit time concept. The mean transit times obtained after lozenge and tablet administration were compared. RESULTS: The variance in absorption phase was significantly higher than that in the distribution/elimination phase in the pharmacokinetic profiles of the lozenge, suggesting additional absorption processes. The mean transit time of the tablet was significantly greater than that of the lozenge, by 7.69 hours with a 90% confidence interval (CI) of 3.11, 12.27. Early drug dissolution/absorption in the oral cavity and gastrointestinal absorption was successfully modelled to the pharmacokinetic profiles after lozenge administration. The additional availability of the drug to systemic circulation was mainly due to complete dissolution in the oral cavity prior to absorption as well as to oral mucosal transport. Between the two processes, dissolution was proposed to be a limiting step, since oral mucosal absorption was at a very high rate. The estimated average dissolution rate constant (90% CI) in first-order fashion was 0.13h(-1) (0.08, 0.32). CONCLUSION: Absorption rates between lozenge and tablet could be differentiated with the aid of the mean transit time concept. However, estimation of oral mucosal absorption was not possible because the blood sampling intervals were not sufficiently frequent.
Authors: W Couet; J Girault; B G Reigner; I Ingrand; J Bizouard; D Acerbi; P Chiesi; J B Fourtillan Journal: Int J Clin Pharmacol Ther Toxicol Date: 1989-09
Authors: R H Epstein; H G Mendel; T A Witkowski; R Waters; K M Guarniari; A T Marr; J B Lessin Journal: Anesth Analg Date: 1996-12 Impact factor: 5.108