Publication

Effect of Food on the Pharmacokinetics of 2 Formulations of DRL-17822, a Novel Selective Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Males

Kruithof, A. C., Kumar, R., Stevens, J., de Kam, M. L., Gautam, A., Alikunju, S., Padhi, B. K., Kulkarni, S., Raghuvanshi, R. S., Gandhi, R., Burggraaf, J. & Kamerling, I. M. C., 10-Jun-2019, In : Clinical pharmacology in drug development. 8, 8, p. 1042-1052 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Kruithof, A. C., Kumar, R., Stevens, J., de Kam, M. L., Gautam, A., Alikunju, S., ... Kamerling, I. M. C. (2019). Effect of Food on the Pharmacokinetics of 2 Formulations of DRL-17822, a Novel Selective Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Males. Clinical pharmacology in drug development, 8(8), 1042-1052. https://doi.org/10.1002/cpdd.707

Author

Kruithof, Annelieke C ; Kumar, Rajinder ; Stevens, Jasper ; de Kam, Marieke L ; Gautam, Anirudh ; Alikunju, Shanavas ; Padhi, Bijay K ; Kulkarni, Swati ; Raghuvanshi, Rajeev S ; Gandhi, Rajesh ; Burggraaf, Jacobus ; Kamerling, Ingrid M C. / Effect of Food on the Pharmacokinetics of 2 Formulations of DRL-17822, a Novel Selective Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Males. In: Clinical pharmacology in drug development. 2019 ; Vol. 8, No. 8. pp. 1042-1052.

Harvard

Kruithof, AC, Kumar, R, Stevens, J, de Kam, ML, Gautam, A, Alikunju, S, Padhi, BK, Kulkarni, S, Raghuvanshi, RS, Gandhi, R, Burggraaf, J & Kamerling, IMC 2019, 'Effect of Food on the Pharmacokinetics of 2 Formulations of DRL-17822, a Novel Selective Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Males', Clinical pharmacology in drug development, vol. 8, no. 8, pp. 1042-1052. https://doi.org/10.1002/cpdd.707

Standard

Effect of Food on the Pharmacokinetics of 2 Formulations of DRL-17822, a Novel Selective Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Males. / Kruithof, Annelieke C; Kumar, Rajinder; Stevens, Jasper; de Kam, Marieke L; Gautam, Anirudh; Alikunju, Shanavas; Padhi, Bijay K; Kulkarni, Swati; Raghuvanshi, Rajeev S; Gandhi, Rajesh; Burggraaf, Jacobus; Kamerling, Ingrid M C.

In: Clinical pharmacology in drug development, Vol. 8, No. 8, 10.06.2019, p. 1042-1052.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Kruithof AC, Kumar R, Stevens J, de Kam ML, Gautam A, Alikunju S et al. Effect of Food on the Pharmacokinetics of 2 Formulations of DRL-17822, a Novel Selective Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Males. Clinical pharmacology in drug development. 2019 Jun 10;8(8):1042-1052. https://doi.org/10.1002/cpdd.707


BibTeX

@article{b8fc4afd9d1141de8bca5fc7474e4ba8,
title = "Effect of Food on the Pharmacokinetics of 2 Formulations of DRL-17822, a Novel Selective Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Males",
abstract = "DRL-17822 is a novel selective cholesteryl ester transfer protein inhibitor that showed an increased exposure, including an increase of >20-fold of maximum concentration and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration, following a high-fat breakfast using a nanocrystal formulation. To reduce this effect of food, we generated an amorphous solid dispersion formulation. In this study, we compared the food effect of both formulations of DRL-17822 in a 2-part randomized, open-label, 4-way crossover study involving healthy adult males 18-45 years of age. In both parts of the study, 12 subjects received both formulations of DRL-17822 in both the fasted and fed states; a low-fat breakfast was provided in the first part and a high-fat breakfast in the second part. Compared to the nanocrystal formulation, the amorphous solid dispersion formulation substantially increased DRL-17822 exposure in the fasted state, including increased maximum concentration, area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration, and area under plasma concentration-time curve from time zero to infinity. Following a high-fat breakfast, DRL-17822 exposure was increased to a lesser extent in the amorphous solid dispersion formulation compared to the nanocrystal formulation (P < .001). Moreover, compared to the nanocrystal formulation the amorphous solid dispersion formulation caused a more pronounced increase in high-density lipoprotein in the fasted state. Consuming breakfast increased the effect of DRL-17822 on high-density lipoprotein. Taken together, our results indicate that by improving its formulation, DRL-17822 has a favorable exposure profile and therefore a more predictable food effect profile.",
keywords = "amorphous solid dispersion formulation, cholesteryl ester transfer protein (CETP) inhibition, DRL-17822, food effect, nanocrystal formulation, pharmacokinetics",
author = "Kruithof, {Annelieke C} and Rajinder Kumar and Jasper Stevens and {de Kam}, {Marieke L} and Anirudh Gautam and Shanavas Alikunju and Padhi, {Bijay K} and Swati Kulkarni and Raghuvanshi, {Rajeev S} and Rajesh Gandhi and Jacobus Burggraaf and Kamerling, {Ingrid M C}",
note = "{\circledC} 2019, The American College of Clinical Pharmacology.",
year = "2019",
month = "6",
day = "10",
doi = "10.1002/cpdd.707",
language = "English",
volume = "8",
pages = "1042--1052",
journal = "Clinical pharmacology in drug development",
issn = "2160-763X",
number = "8",

}

RIS

TY - JOUR

T1 - Effect of Food on the Pharmacokinetics of 2 Formulations of DRL-17822, a Novel Selective Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Males

AU - Kruithof, Annelieke C

AU - Kumar, Rajinder

AU - Stevens, Jasper

AU - de Kam, Marieke L

AU - Gautam, Anirudh

AU - Alikunju, Shanavas

AU - Padhi, Bijay K

AU - Kulkarni, Swati

AU - Raghuvanshi, Rajeev S

AU - Gandhi, Rajesh

AU - Burggraaf, Jacobus

AU - Kamerling, Ingrid M C

N1 - © 2019, The American College of Clinical Pharmacology.

PY - 2019/6/10

Y1 - 2019/6/10

N2 - DRL-17822 is a novel selective cholesteryl ester transfer protein inhibitor that showed an increased exposure, including an increase of >20-fold of maximum concentration and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration, following a high-fat breakfast using a nanocrystal formulation. To reduce this effect of food, we generated an amorphous solid dispersion formulation. In this study, we compared the food effect of both formulations of DRL-17822 in a 2-part randomized, open-label, 4-way crossover study involving healthy adult males 18-45 years of age. In both parts of the study, 12 subjects received both formulations of DRL-17822 in both the fasted and fed states; a low-fat breakfast was provided in the first part and a high-fat breakfast in the second part. Compared to the nanocrystal formulation, the amorphous solid dispersion formulation substantially increased DRL-17822 exposure in the fasted state, including increased maximum concentration, area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration, and area under plasma concentration-time curve from time zero to infinity. Following a high-fat breakfast, DRL-17822 exposure was increased to a lesser extent in the amorphous solid dispersion formulation compared to the nanocrystal formulation (P < .001). Moreover, compared to the nanocrystal formulation the amorphous solid dispersion formulation caused a more pronounced increase in high-density lipoprotein in the fasted state. Consuming breakfast increased the effect of DRL-17822 on high-density lipoprotein. Taken together, our results indicate that by improving its formulation, DRL-17822 has a favorable exposure profile and therefore a more predictable food effect profile.

AB - DRL-17822 is a novel selective cholesteryl ester transfer protein inhibitor that showed an increased exposure, including an increase of >20-fold of maximum concentration and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration, following a high-fat breakfast using a nanocrystal formulation. To reduce this effect of food, we generated an amorphous solid dispersion formulation. In this study, we compared the food effect of both formulations of DRL-17822 in a 2-part randomized, open-label, 4-way crossover study involving healthy adult males 18-45 years of age. In both parts of the study, 12 subjects received both formulations of DRL-17822 in both the fasted and fed states; a low-fat breakfast was provided in the first part and a high-fat breakfast in the second part. Compared to the nanocrystal formulation, the amorphous solid dispersion formulation substantially increased DRL-17822 exposure in the fasted state, including increased maximum concentration, area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration, and area under plasma concentration-time curve from time zero to infinity. Following a high-fat breakfast, DRL-17822 exposure was increased to a lesser extent in the amorphous solid dispersion formulation compared to the nanocrystal formulation (P < .001). Moreover, compared to the nanocrystal formulation the amorphous solid dispersion formulation caused a more pronounced increase in high-density lipoprotein in the fasted state. Consuming breakfast increased the effect of DRL-17822 on high-density lipoprotein. Taken together, our results indicate that by improving its formulation, DRL-17822 has a favorable exposure profile and therefore a more predictable food effect profile.

KW - amorphous solid dispersion formulation

KW - cholesteryl ester transfer protein (CETP) inhibition

KW - DRL-17822

KW - food effect

KW - nanocrystal formulation

KW - pharmacokinetics

U2 - 10.1002/cpdd.707

DO - 10.1002/cpdd.707

M3 - Article

C2 - 31183985

VL - 8

SP - 1042

EP - 1052

JO - Clinical pharmacology in drug development

JF - Clinical pharmacology in drug development

SN - 2160-763X

IS - 8

ER -

ID: 85444357