Pharmacokinetics, absorption, and excretion of radiolabeled revexepride: a Phase I clinical trial using a microtracer and accelerator mass spectrometry-based approach

Figures & data

Figure 1 Study flow and timeline.

Table 1 Study demographics and participant characteristics

Characteristic	Participants (n=6)
Age (years), mean (SD)	29.5 (2.07)
Sex, n (%)
Male	6 (100)
Ethnicity, n (%)
Not Hispanic or Latino	6 (100)
Race, n (%)
Caucasian	5 (83.3)
Afro-Caribbean	1 (16.7)
BMI (kg/m^2), mean (SD)	25.0 (2.11)

Notes: Three participants had protocol violations: one had a blood sample drawn 7 minutes late owing to an adverse event, and two had samples that were not spun within the required 15 minutes.

Abbreviations: BMI, body mass index; SD, standard deviation.

Table 2 Mean data for urinary and fecal ¹⁴C dose excretion

Time (hours)	Radioactivity recovered from urine (%)		Time (hours)	Radioactivity recovered from urine (%)
	Mean	SD		Mean	SD
0–2	2.50	1.05	0–24	21.80	14.10
2–4	6.02	1.52
4–8	9.28	3.55
8–12	5.51	1.98
12–24	7.62	2.05
24–48	5.07	1.79	24–48	20.20	8.60
48–72	1.39	0.84	48–72	13.70	6.22
72–96	0.39	0.23	72–96	4.34	3.50
96–120	0.15	0.07	96–120	0.19	0.15
120–144	0.08	0.04	120–144	0.84	1.28
144–168	0.05	0.03	144–168	0.22	0.19
168–192	0.05	0.02	168–192	0.09	0.08
192–216	0.04	0.02	192–216	0.04	0.04
216–240	0.04	0.01	216–240	0.04	0.04
Total	38.20	10.30	Total	57.30	10.40

Abbreviation: SD, standard deviation.

Figure 2 Mean cumulative percent of radioactive dose recovered in urine and feces following administration of a single dose of 2 mg [¹⁴C]revexepride to healthy male volunteers in the pharmacokinetic analysis set (linear scale).

Note: Error bars are presented as ± standard deviation and have been staggered.

Figure 3 Concentration of total radioactivity in blood and plasma and revexepride in plasma.

Notes: The lower limit of quantification for LC–MS/MS was lower than that of the assays used to determine total radioactivity, allowing plasma revexepride to be monitored for a longer period of time following administration.
Abbreviation: LC–MS/MS, liquid chromatography–mass spectrometry/mass spectrometry.

Table 3 Pharmacokinetic parameter data in whole blood and plasma

Analyte	Cmax (ng Eq/mL)	Tmax (hours)	AUC0−∞ (ng Eq·h/mL)	t1/2 (hours)	Vz/F (L)	CL/F (L/h)
Radioactivity in plasma	11.66±3.54 (11.28)	1.83±1.13 (1.62)	137.31±56.10 (130.41)	10.9±2.54 (10.6)	NC	NC
Radioactivity in whole blood	9.25±2.14 (9.06)	2.17±1.03 (1.98)	101.96±41.58 (95.98)	6.96±1.51 (6.82)	NC	NC
Revexepride in plasma	4.64±0.89 (4.58)	1.75±1.17 (1.51)	43.48±13.80 (41.76)	11.0±2.38 (10.8)	828±118	49.8±15.2

Note: Values are arithmetic mean ± standard deviation (geometric mean).

Abbreviations: AUC_0−∞, area under the concentration–time curve from time 0 extrapolated to infinity; CL/F, plasma clearance; C_max, maximum concentration; Eq, equivalent; NC, not calculated; t_1/2, mean elimination half-life; T_max, time to C_max; V_z/F, volume of distribution.