Bayesian approach for the estimation of cyclosporine area under the curve using limited sampling strategies in pediatric hematopoietic stem cell transplantation

Sarem, Sarem; Li, Jun; Barriere, Olivier; Litalien, Catherine; Théorêt, Yves; Lapeyraque, Anne-Laure; Nekka, Fahima

doi:10.1186/1742-4682-11-39

Theoretical Biology and Medical Modelling

Table 3 Performance of B-LSS for the prediction of observed and ‘underlying’ AUC using selected Pop-PK models

From: Bayesian approach for the estimation of cyclosporine area under the curve using limited sampling strategies in pediatric hematopoietic stem cell transplantation

	LSS #	Concentration-time points	Error indices (for observed AUC)						Error index for ‘underlying’ AUC
			RMSE% (Confidence interval)	ME% (Confidence interval)	E%			95^thPAE%:	95^thPAE%:
			RMSE% (Confidence interval)	ME% (Confidence interval)	<-20%	[-20%, 20%]	>20%	95^thPAE%:	95^thPAE%:
IV	1	C2, C2.5, C8, C10	4.39(3.26, 5.28)	1.19(-0.67, 3.06)	0	23	0	7	14
	2	C0, C2, C3, C4	7.30(4.37, 9.36)	1.93(-1.18, 5.04)	0	23	0	14	17
	3	C0, C2, C2.5, C3	7.71(4.32, 10.01)	1.75(-1.57, 5.07)	0	22	1	15	17
	4	C0, C2, C2.5, C4	7.61(2.33, 10.51)	2.83(-0.30, 5.95)	0	22	1	16	19
	5	C2, C2.5, C8	5.70(4.30, 6.81)	3.24(1.17, 5.31)	0	23	0	10	17
	6	C0, C2, C3	8.14(4.63, 10.54)	2.40(-1.04, 5.84)	0	22	1	16	19
	7	C0, C2.5, C3	9.85(7.16, 11.95)	-0.61(-4.96, 3.73)	0	23	0	18	14
	8	C0, C2.5, C4	9.53(6.42, 11.85)	0.89(-3.30, 5.09)	0	23	0	19	16
	9	C2.5, C8	8.64(6.49, 10.36)	0.58(-3.24, 4.39)	0	23	0	15	14
	10	C0, C2.5	11.33(8.25, 13.74)	1.05(-3.93, 6.04)	1	22	0	20	19
	11	C0, C3	11.42(8.55, 13.69)	-0.94(-5.97, 4.09)	1	22	0	20	15
	12	C0, C4	12.11(8.19, 15.04)	2.65(-2.58, 7.87)	1	21	1	25	19
	13	C4	13.88(10.30, 16.71)	4.36(-1.46, 10.19)	1	18	4	23	25
	14	C0	23.32(16.81, 28.37)	0.55(-9.75, 10.86)	6	10	7	40	38
PO	15	C1.5, C3, C4, C8	6.98(5.29, 8.33)	-3.20(-5.24, -1.17)	0	39	0	14	16
	16	C0, C1.5, C2, C4	7.50(4.97, 9.36)	0.70(-1.76, 3.15)	0	38	1	16	11
	17	C0, C1.5, C3, C4	7.60(5.48, 9.25)	-0.35(-2.85, 2.14)	0	39	0	16	14
	18	C0, C1, C3, C4	9.34(6.62, 11.42)	0.43(-2.63, 3.50)	1	38	0	18	16
	19	C0.5, C3, C4	11.73(7.27, 14.91)	0.08(-3.77, 3.93)	1	38	0	18	15
	20	C0, C2, C4	11.02(8.00, 13.37)	3.40(-0.04, 6.84)	1	36	2	24	19
	21	C0, C1, C4	10.26(6.11, 13.15)	0.48(-2.89, 3.84)	1	37	1	24	20
	22	C0, C1, C3	13.08(9.20, 16.04)	2.07(-2.17, 6.31)	2	34	3	28	21
	23	C1, C4	11.96(8.36, 14.70)	-2.86(-6.68, 0.95)	4	34	1	25	25
	24	C0, C3	18.65(11.05,23.94)	2.16(-3.92, 8.24)	4	31	4	41	34
	25	C0, C4	21.37(16.26,25.47)	2.09(-4.89, 9.07)	6	23	10	43	38
	26	C0, C2	21.19(12.55,27.21)	8.61(2.25, 14.97)	2	29	8	44	36
	27	C3	17.46(12.77,21.14)	-3.17(-8.81, 2.47)	7	29	3	33	30
	28	C0	43.26(31.81,52.26)	15.62(2.37, 28.87)	7	14	18	86	87

The selected Pop-PK models are the structural model with combined errors (Model 4 in Table 2) and the one with additive errors (Model 6 in Table 2) for IV and PO CsA, respectively.
C_t: concentration at time t in hours post-dose, ME%: relative mean prediction error, RMSE%: relative root mean squared prediction error, 95^th APE%: 95^th percentile of the absolute relative errors.

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