Lamivudine versus Sorbitol
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Study Design
This was an open label, randomized crossover study in (n=37) healthy adult subjects. Participants were randomized to receive each treatment in 1 of 4 sequences with greater than or equal to a week’s washout period. Treatment groups include a single dose of lamivudine (3TC) 300mg, 3TC 300mg + sorbitol 3.2g, 3TC 300mg + sorbitol 10.2g or 3TC 300mg + sorbitol 13.4g. 3TC was provided as a 10mg/ml oral solution following an 8 hour fast. PK analysis samples were collected after each treatment, test/reference geometric least squares means ratio and 90% CI were determined.
Study Results
Of 37 subjects screened, 16 were randomized and completed the study. Selected 3TC PK parameters and statistical comparisons to reference are summarized in the Table.
Sorbitol had a dose-dependent effect on 3TC PK with 28%, 52%, and 55% lower Cmax, 20%, 39%, and 44% lower AUC(0-24), and 14%, 32%, and 36% lower AUC(0-∞) when
co-administered with 3.2 g, 10.2 g, and 13.4 g sorbitol, respectively. The median 3TC Tmax occurred between 0.75 to 1.26 h post dose, with later Tmax associated with sorbitol coadministration.
3TC with and without sorbitol containing solutions were well tolerated. There were no deaths or SAEs. A total of 3 subjects reported 5 AEs; 1 was drug-related.
Study Conclusions
: Co-administration of single doses of 3TC and sorbitol solutions under fasted conditions resulted in decreased 3TC plasma exposures. Sorbitol had the greatest impact
on 3TC Cmax and AUC(0-24), suggesting that an absorption-based interaction is the likely mechanism for the reduction in 3TC exposures observed in this study.
References
Adkinson KK, McCaig C, Wolstenholme A, Lou Y, Zhang Z, Eld A, Hayward K, Schaefer M. Effect of sorbitol on 3tc pk after administration of lamivudine solution in adult . Conference On Retroviruses And Opportunistic Infections. Seattle, WA, USA. 2017; February 2017.
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