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Effect of Sorbitol on the Pharmacokinetic Profile of Lamivudine Oral Solution in Adults: An Open‐Label, Randomized Study
Author(s) -
Adkison Kimberly,
Wolstenholme Allen,
Lou Yu,
Zhang Zhiping,
Eld Amy,
Perger Teodora,
Vangerow Harald,
Hayward Katy,
Shaefer Mark,
McCoig Cynthia
Publication year - 2018
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.943
Subject(s) - lamivudine , cmax , crossover study , bioavailability , sorbitol , pharmacokinetics , pharmacology , medicine , chemistry , placebo , food science , virology , virus , hepatitis b virus , alternative medicine , pathology
In children aged ≤4 years, the relative bioavailability of lamivudine oral solution was 37% lower than that of a tablet formulation. An open‐label, four‐way crossover study was conducted in healthy adults to evaluate the effect of sorbitol, a common liquid excipient, on the pharmacokinetics of lamivudine oral solution ( ClinicalTrials.gov identifier, NCT02634073). Sixteen subjects were randomized to one of four sequences consisting of four doses of lamivudine 300 mg (10 mg/mL) alone or with sorbitol 3.2, 10.2, or 13.4 g. Sorbitol 3.2, 10.2, and 13.4 g decreased lamivudine maximum concentration ( C max ) by 28%, 52%, and 55% and area under the concentration–time curve from time 0 to 24 h (AUC 0‐24 ) by 20%, 39%, and 44%, respectively. Three subjects (19%) reported five nonserious adverse events (one drug‐related). The dose‐dependent effects of sorbitol on lamivudine C max and AUC 0‐24 reveal an absorption‐based interaction that may decrease lamivudine exposure in patients coadministered sorbitol‐containing medicines.