Lack of Effect of Cenerimod, a Selective S1P1 Receptor Modulator, on the Pharmacokinetics of a Combined Oral Contraceptive
Abstract
:1. Introduction
2. Results
2.1. Disposition and Demographics
2.2. PK
2.3. Effect of Cenerimod on the PK of Levonorgestrel
2.4. Effect of Cenerimod on the PK of EE
2.5. Safety and Tolerability
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Study Population
4.3. Study Conduct
4.4. Drug Selection
4.5. PK Assessments
4.6. Safety and Tolerability Assessments
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Statistic | Cenerimod 0.5 mg (N = 10) | Cenerimod 4 mg (N = 14) | Overall (N = 24) | |
---|---|---|---|---|
Sex | ||||
Female | n (%) | 4 (40.0 %) | 5 (35.7 %) | 9 (37.5 %) |
Male | n (%) | 6 (60.0 %) | 9 (64.3 %) | 15 (62.5 %) |
Age (years) | Mean (SD) | 49.5 (15.06) | 43.2 (13.93) | 45.8 (14.44) |
Range | 26–65 | 24–64 | 24–65 | |
Weight (kg) 1 | Mean (SD) | 68.46 (12.799) | 70.51 (10.190) | 69.65 (11.129) |
Range | 45.8–90.1 | 50.6–83.8 | 45.8–90.1 | |
Height (cm) | Mean (SD) | 171.3 (11.53) | 171.6 (9.29) | 171.5 (10.04) |
Range | 151–186 | 154–185 | 151–186 | |
BMI (kg/m2) | Mean (SD) | 23.24 (3.290) | 23.93 (2.840) | 23.64 (2.986) |
Range | 20.1–29.8 | 20.0–28.9 | 20.0–29.8 |
PK of Levonorgestrel | Effect of Cenerimod on the PK of Levonorgestrel | ||||
---|---|---|---|---|---|
COC alone | COC + cenerimod 0.5 mg | COC + cenerimod 4 mg | COC + cenerimod 0.5 mg vs. COC alone | COC + cenerimod 4 mg vs. COC alone | |
(N = 24) | (n = 10) | (n = 9) | |||
Cmax (pg/mL) | 1571 (1195–2066) | 1778 (1153–2742) | 1597 (1038–2456) | 1.11 (0.98–1.26) | 1.06 (0.93–1.21) |
0.1538 | 0.4404 | ||||
tmax (h) | 1.00 (1.00–3.00) | 1.00 (1.00–2.00) | 1.00 (1.00–2.00) | NC | NC |
AUC0–t (h·pg/mL) | 15,307 (11,129–21,055) | 17,876 (11,145–28,673) | 17,930 (10,034–32,038) | 1.18 (1.11–1.25) | 1.22 (1.14–1.30) |
0.0002 | <.0001 | ||||
AUC0–∞ (h·pg/mL) | 17,395 (12,728–23,772) | 20,084 (12,852–31,386) | 20,570 (11,831–35,764) | 1.17 (1.10–1.25) | 1.25 (1.17–1.34) |
0.0004 | <.0001 | ||||
t½ (h) | 27.4 (23. 5–31.9) | 28.4 (23.5–34.4) | 28.9 (22.6–36.9) | 1.00 (0.92–1.09) | 1.12 (1.02–1.23) |
0.9655 | 0.0445 |
PK of Ethinylestradiol | Effect of Cenerimod on the PK of Ethinylestradiol | ||||
---|---|---|---|---|---|
COC alone | COC + cenerimod 0.5 mg | COC + cenerimod 4 mg | COC + cenerimod 0.5 mg vs. COC alone | COC + cenerimod 4 mg vs. COC alone | |
(N = 24) | (n = 10) | (n = 9) | |||
Cmax (pg/mL) | 31.1 (26.1–37.2) | 32.1 (21.7–47.5) | 32.1 (24.0–42.9) | 0.98 (0.85–1.14) | 1.08 (0.92–1.26) |
0.8480 | 0.4100 | ||||
tmax (h) | 1.00 (1.00–3.00) | 2.00 (1.00–3.00) | 1.00 (1.00–3.00) | NC | NC |
AUC0–t (h·pg/mL) | 266 (205–345) | 285 (169–483) | 270 (195–374) | 1.10 (0.95–1.27) | 1.04 (0.90–1.21) |
0.2603 | 0.6447 | ||||
AUC0–∞ (h·pg/mL) | 334 (269–416) | 345 (212–563) | 325 (237–447) | 1.03 (0.92–1.16) | 1.00 (0.89–1.13) |
0.6581 | 0.9798 | ||||
t½ (h) | 12.1 (10.1–14.5) | 10.7 (6.94–16.4) | 10.6 (7.06–15.8) | 0.92 (0.81–1.06) | 0.88 (0.76–1.01) |
0.3182 | 0.1324 |
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Juif, P.-E.; Mueller, M.S.; Charfi, H.; Dingemanse, J. Lack of Effect of Cenerimod, a Selective S1P1 Receptor Modulator, on the Pharmacokinetics of a Combined Oral Contraceptive. Int. J. Mol. Sci. 2022, 23, 14986. https://doi.org/10.3390/ijms232314986
Juif P-E, Mueller MS, Charfi H, Dingemanse J. Lack of Effect of Cenerimod, a Selective S1P1 Receptor Modulator, on the Pharmacokinetics of a Combined Oral Contraceptive. International Journal of Molecular Sciences. 2022; 23(23):14986. https://doi.org/10.3390/ijms232314986
Chicago/Turabian StyleJuif, Pierre-Eric, Markus S. Mueller, Hakim Charfi, and Jasper Dingemanse. 2022. "Lack of Effect of Cenerimod, a Selective S1P1 Receptor Modulator, on the Pharmacokinetics of a Combined Oral Contraceptive" International Journal of Molecular Sciences 23, no. 23: 14986. https://doi.org/10.3390/ijms232314986