Population pharmacokinetic modeling of flurbiprofen, the active metabolite of flurbiprofen axetil, in Chinese patients with postoperative pain

Figures & data

Table 1 Demographics of the study population (n=72)

	Mean ± SD	Median	Range
Age (years)	50.50±13.63	50	18–72
Sex (F:M)	45:27
Body weight (kg)	67.47±11.46	68.50	45–96
Height (cm)	164.50±9.08	165	149–185
Body-mass index (kg/cm^2)	24.89±3.49	24.33	16.94–34.08
Flurbiprofen dose (mg)	67.47±11.46	68.50	45–96
Plasma flurbiprofen concentration (μg/mL)	8.302±2.847	7.915	3.48–14.56
CSF flurbiprofen concentration (ng/mL)	5.583±3.655	5.300	0–20.80

Note: Data from Zhang et al.⁶

Abbreviation: CSF, cerebrospinal fluid.

Figure 1 DVs vs individual predicted data (IPRED) (A) and predicted data (PRED) (B).

Abbreviations: C_obs, flurbiprofen concentration in plasma; CSF_obs, flurbiprofen concentration in cerebrospinal fluid; DVs, detected values; IPRED, individual predicted data; PRED, predicted data.

Figure 2 CWRes vs predicted data (PRED) (A) and time after dose (B).

Abbreviations: C_obs, flurbiprofen concentration in plasma; CSF_obs, flurbiprofen concentration in cerebrospinal fluid; CWRes, conditional weighted residuals; PRED, predicted data.

Table 2 Population pharmacokinetic parameters of flurbiprofen for basic and final models

	Estimate	SE	CV (%)	95% CI
Basic model
θKe (L/h)	0.0015	1.92^−9	0.0001	0.0015–0.0015
θVd (L)	7.95	0.0357	0.4491	7.88–8.02
θCL (L/h)	1.51	0.0013	0.0847	1.509–1.514
ωKe (%)	0.0871
ωVd (%)	0.0986
ωCL (%)	0.7097
σ	0.0024	1.01^−5	0.4132	0.0024–0.0024
Final model
θKe (/h)	0.0015	1.32^−9	8.75^−5	0.0015–0.0015
θVd (L)	7.91	0.0408	0.5159	7.83–7.99
θCL (L/h)	1.55	0.0017	0.1068	1.543–1.550
θweight	−0.0080	2.11^−5	−0.2621	−0.0081 to −0.0080
θheight	−0.0162	8.12^−9	−5.00^−5	−0.0162 to −0.0162
ωKe (%)	0.0220
ωVd (%)	0.0890
ωCL (%)	0.8275
σ	0.0023	6.66^−6	0.2944	0.0023–0.0023

Abbreviations: SE, standard error; CV, coefficient of variation.

Figure 3 Final-model population Eta QQ plot.

Notes: (A) n_CL; (B) n_Ke; (C) n_Vd.

Figure 4 Prediction-corrected visual predictive check for the final flurbiprofen model on logarithmic scale.

Notes: (A) Flurbiprofen concentration in plasma; (B) flurbiprofen concentration in cerebrospinal fluid.
Abbreviation: DV, detected value.

Table 3 Results of bootstrap analysis

Parameter	Final-model estimate	Bootstrap estimate
		Estimate	95% CI	CV (%)
θKe (/h)	0.0015	0.0015	0.0015 to 0.0015	8.75e^−5
θVd (L)	7.91	7.91	7.83 to 7.99	0.5159
θCL (L/h)	1.55	1.55	1.54 to 1.55	0.1069
θweight	−0.0080	−0.0080	−0.0081 to −0.0080	−0.2621
θheight	−0.0162	−0.0162	−0.0162 to −0.0162	−5.00e^−5
ωKe (%)	0.0220
ωVd (%)	0.0890
ωCL (%)	0.8275
σ	0.0023	0.0023	0.0023 to 0.0023	0.2944

Abbreviation: CV, coefficient of variation.

ZhangHGuJFengYAnHAbsorption kinetics of flurbiprofen axetil microspheres in cerebrospinal fluid: A pilot studyInt J Clin Pharmacol Ther2017551187588028956529

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