Improved Bioavailability of MELTDOSE Once-Daily Formulation of Tacrolimus (LCP-Tacro) with Controlled Agglomeration Allows for Consistent Absorption over 24 Hrs: A Scintigraphic and Pharmacokinetic Evaluation
Veloxis Pharmaceuticals, Edison, NJ
Meeting: 2013 American Transplant Congress
Abstract number: B1034
MeltDose® is a process technology intended to enhance oral bioavailability of poorly water soluble compounds. We evaluated the transit time, pharmacokinetic (PK) profile and site of release of tacrolimus from a controlled release once-daily formulation (LCP-Tacro™) with controlled agglomeration MeltDose technology and assessed inter- and intra-subject variability. This was a single dose, 2-way, open-label, replicate design, Phase 1, pharmacoscintigraphic study. A radiolabelled 2 mg LCP-Tacro tablet was administered to the same 8 subjects on two occasions, with a 14 day washout between dosing. Blood samples and scintigraphic images were collected at 36, 48 and 72 hours post-dose. The transit of LCP-Tacro was similar on study periods 1 and 2. Initial disintegration of the formulation tended to occur in the stomach and/or proximal small bowel and complete disintegration tended to occur in the distal small bowel or colon. Correlation of Tlag values and time to initial tablet disintegration confirmed that initial drug release is likely to be via diffusion. The Cmax values were similar for the two dosing periods. The mean Cmax value was 3.88 ± 0.93 ng/mL for study period 1 and 3.36 ± 1.40 ng/mL for study period 2. The mean AUC0-∞ were 149.53 ± 22.89 ng.h/mL for study period 1 and 120.40 ± 52.06 ng.h/mL for study period 2.
Study Period 1 | Study Period 2 | |
Gastric emptying (hrs post-dose) | 1.13 (0.99) | 0.95 (0.74) |
Colon arrival (hrs post-dose) | 3.41 (1.23) | 4.82 (1.18) |
Small intestinal transit (hrs) | 2.70 (1.25) | 4.05 (1.68) |
Initial disintegration | 0.69 (0.59) | 1.03 (0.81) |
Complete disintegration | 8.48 (9.61) | 9.37 (5.34) |
Cmax | 3.88 (0.93) | 3.36 (1.40) |
t½ (hours) | 40.48 ± 14.24 (35.2%) | 37.60 ± 10.72 (28.5%) |
AUC0-∞ (ng.h/mL) | 149.53 (22.89) | 120.40 (52.06) |
Tmax (median, range) | 6.67 (0.50 – 12.00) | 6.75 (0.50 – 8.00) |
There were no serious or severe AEs; no subjects discontinued because of a treatment related AE. There were no clinically significant changes in vital signs or ECGs. Using Veloxis proprietary MeltDose technology in the LCP-Tacro formulation modifies the absorption characteristics in a manner that would allow for a once-daily sustained release PK profile and enhanced bioavailability.
Nigro, V.: Employee, Veloxis Pharmaceuticals. Glicklich, A.: Employee, Veloxis Pharmaceuticals. Weinberg, J.: Employee, Veloxis Pharmaceuticals.
To cite this abstract in AMA style:
Nigro V, Glicklich A, Weinberg J. Improved Bioavailability of MELTDOSE Once-Daily Formulation of Tacrolimus (LCP-Tacro) with Controlled Agglomeration Allows for Consistent Absorption over 24 Hrs: A Scintigraphic and Pharmacokinetic Evaluation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/improved-bioavailability-of-meltdose-once-daily-formulation-of-tacrolimus-lcp-tacro-with-controlled-agglomeration-allows-for-consistent-absorption-over-24-hrs-a-scintigraphic-and-pharmacokinetic-ev/. Accessed December 5, 2024.« Back to 2013 American Transplant Congress