Bioequivalence of a new liquid formulation of ursodeoxycholic acid (Ursofalk suspension) and Ursofalk capsules measured by plasma pharmacokinetics and biliary enrichment.
BACKGROUND
Ursodeoxycholic acid is an approved therapy for hepatobiliary disorders but in infants and children compliance is compromised because it is formulated exclusively as capsules, or tablets.


OBJECTIVE
To determine the pharmacokinetics and bioequivalence of a new liquid formulation of ursodeoxycholic acid (Ursofalk suspension) with a standard capsule (Ursofalk) in a randomized, unblinded, crossover designed study of 24 healthy adults.


METHODS
Equivalence was based on single bolus oral plasma pharmacokinetics and biliary ursodeoxycholic acid enrichments after repeat doses. Biliary bile acid composition and hydrophobicity index were also compared. Ursodeoxycholic acid was measured in duodenal bile by high-performance liquid chromatography and in plasma by mass spectrometry.


RESULTS
The mean percentage biliary ursodeoxycholic acid enrichment after administration of the suspension was not significantly different from that obtained with capsules (44.2 +/- 11.7% vs. 46.9 +/- 10.2%, respectively). The equivalence ratio was 0.94 (95% CI: 0.8-1.1), establishing bioequivalence between suspension and capsules. Both formulations reduced the biliary hydrophobicity index and no differences in bile acid composition were observed between formulations. The plasma pharmacokinetics of both formulations was similar and the tolerability of the suspension was excellent.


CONCLUSIONS
A new liquid formulation of ursodeoxycholic acid suitable for paediatric patients is pharmacologically bioequivalent to capsules when given as single, or repeated oral doses.
Setchell
K D R
KD
Department of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. kenneth.setchell@cchmc.org
Galzigna
L
L
O'Connell
N
N
Brunetti
G
G
Tauschel
H-D
HD
D000293:Adolescent; D000328:Adult; D001646:Bile / Q000737:chemistry; D001647:Bile Acids and Salts / Q000097:blood; D002214:Capsules; D002756:Cholagogues and Choleretics / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D013810:Therapeutic Equivalency; D014580:Ursodeoxycholic Acid / Q000493:pharmacokinetics*
D001647:Bile Acids and Salts; D002214:Capsules; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid