Prediction of absolute bioavailability for drugs using oral and renal clearance following a single oral dose: a critical view.
In order to determine the absolute bioavailability, both oral and intravenous administrations of a drug are often used. Recently a new method has been proposed to determine absolute bioavailability in the absence of intravenous dose. Following a single oral dose, this method requires oral and renal clearance data from normal subjects and renal failure patients. The bioavailability is calculated from a plot of oral against renal clearance following an oral dose, where the inverse of the slope is equal to absolute bioavailability. This study examines the prediction of absolute bioavailability from the proposed method for eight drugs which have a wide range of oral and renal clearance. From this study, it appears that the proposed method may not be reliable for the prediction of absolute bioavailability and further investigation is needed to test the validity of this method.
Mahmood
I
I
Division of Pharmaceutical Evaluation I, Food and Drug Administration, Rockville, MD 20852, USA.
D000070:Acebutolol / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000584:Amiloride / Q000493:pharmacokinetics; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics* / Q000652:urine; D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D001262:Atenolol / Q000493:pharmacokinetics; D001682:Biological Availability; D004232:Diuretics / Q000493:pharmacokinetics* / Q000652:urine; D015365:Enoxacin / Q000493:pharmacokinetics; D005424:Flecainide / Q000493:pharmacokinetics; D006635:Histamine H2 Antagonists / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism*; D008875:Middle Aged; D011899:Ranitidine / Q000493:pharmacokinetics; D051437:Renal Insufficiency / Q000378:metabolism / Q000652:urine; D008625:Tiopronin / Q000493:pharmacokinetics
D000889:Anti-Arrhythmia Agents; D000890:Anti-Infective Agents; D004232:Diuretics; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D015365:Enoxacin; D001262:Atenolol; D000070:Acebutolol; D000584:Amiloride; D011899:Ranitidine; D008625:Tiopronin; D005424:Flecainide; C032151:cifenline