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document
Clinical pharmacokinetics of buffered propranolol sublingual tablet ( Promptol™ ) -application of a new " physiologically based " model to assess absorption and disposition . Sublingual administration of certain buffered propranolol may improve the rate and extent of absorption compared to oral administration . The main objectives of this study were to ( 1 ) compare the plasma propranolol concentrations ( Cp-prop ) following sublingual administration of a specially buffered formulation ( Promptol™ ) to that following oral administration of Inderal ( ® ) and ( 2 ) evaluate the utility of a special pharmacokinetic model in describing the Cp-prop following sublingual administration . Eighteen healthy volunteers received 10 mg sublingual Promptol™ or oral Inderal ( ® ) . Multiple Cp-prop were determined and their pharmacokinetics compared . Additional data following sublingual 40 mg Promptol™ or Inderal ( ® ) were utilized for evaluation of a special advanced compartmental absorption and transit ( ACAT ) model . For model simulation , the physicochemical parameters were imported from AMET predictor , whereas the pharmacokinetic parameters were calculated and optimized by Gastroplus ( ® ) . Based on this model , the quantity of drug absorbed via buccal/sublingual mucosa was estimated . Cp-prop was higher at earlier times with 3-fold greater relative bioavailability following sublingual Promptol™ compared to that from oral Inderal ( ® ) . The special ACAT model provided excellent goodness of fit of Cp-prop-time curve and estimated a 56.6 % increase in absorption rate from Promptol™ and higher initial Cp-prop compared to the regular formulation . The modified ACAT model provided a useful approach to describe sublingual absorption of propranolol and clearly demonstrated an improvement of absorption of Promptol™ . The sublingual 10 mg Promptol™ achieved not only a similar systemic exposure as 30 mg oral Inderal ( ® ) but an earlier effective Cp-prop which may be advantageous for certain clinical conditions .
59197
Intervention_Pharmacological
propranolol
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Intervention_Pharmacological
propranolol
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Intervention_Pharmacological
Promptol™
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Intervention_Pharmacological
Inderal
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Intervention_Pharmacological
Promptol™
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Participant_Condition
administration
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Participant_Sample-size
Eighteen
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Participant_Condition
healthy