Table 4. Predicted and observeda buprenorphine pharmacokinetic parameters following administration of sublingual solution
Clinical trial
Dose (mg)
Route of administration
n
Female (%)
Mean age [range] (years)
AUCb (ng×h mL-1)
CL/F (L h-1) Cmax (ng mL-1)
Tmax (h)
Mendelson et al.50 2 sublingual, solution (3 min hold) 6 16.7 29 (21–38) Predicted 9.36 213.6 1.94 1.11
Observed 14.3c 139.9d 1.60c 1.25c
P/O ratio 0.65 1.53 1.21 0.89
Mendelson et al.50 2 sublingual, solution (5 min hold) 6 16.7 29 (21–38) Predicted 9.36 213.6 1.94 1.11
Observed 13.2c 151.5d 1.72c 1.62c
P/O ratio 0.71 1.41 1.13 0.69
Kuhlman et al.41 4 sublingual, solution 6 0.0 34.4 (27–40) Predicted 17.1 233.6 3.28 1.15
Observed 15.0 266.5 3.22 0.60
P/O ratio 1.14 0.88 1.02 1.92
Nath et al.27 8 sublingual, solution 6 0.0 28 (23–42) Predicted 28.9 277.0 5.19 1.14
Observed 34.6 230.9 6.72 1.02
P/O ratio 0.84 1.20 0.77 1.12
Chawarski et al.25 8 sublingual, solution, m.d. 18 29.5 37.8 Predicted 35.0 239.2 6.38 1.12
Observed 25.4 315.6 3.19 1.18
P/O ratio 1.38 0.76 2.00 0.95
Chawarski et al.25 12 sublingual, solution, m.d. 19 29.5 37.8 Predicted 47.3 268.0 8.27 1.12
Observed 33.7 356.0 4.50 0.98
P/O ratio 1.40 0.75 1.84 1.14
Chawarski et al.25 16 sublingual, solution, m.d. 20 29.5 37.8 Predicted 58.1 292.8 9.80 1.12
Observed 36.4 439.4 4.91 1.10
P/O ratio 1.60 0.67 2.00 1.02
Geo. meane 1.05 0.98 1.34 1.06
(95% CI) (0.75–1.46) (0.72–1.33) (0.95–1.90) (0.79–1.41)
AUC, area under the curve; CI, confidence interval; CL/F, apparent clearance; Cmax, peak concentration; m.d., multiple doses; P/O ratio, ratio between predicted and observed value; Tmax, time to reach Cmax. AUC, area under the curve; CI, confidence interval; CL/F, apparent clearance; Cmax, peak concentration; m.d., multiple doses; P/O ratio, ratio between predicted and observed value; Tmax, time to reach Cmax. AUC, area under the curve; CI, confidence interval; CL/F, apparent clearance; Cmax, peak concentration; m.d., multiple doses; P/O ratio, ratio between predicted and observed value; Tmax, time to reach Cmax. AUC, area under the curve; CI, confidence interval; CL/F, apparent clearance; Cmax, peak concentration; m.d., multiple doses; P/O ratio, ratio between predicted and observed value; Tmax, time to reach Cmax. AUC, area under the curve; CI, confidence interval; CL/F, apparent clearance; Cmax, peak concentration; m.d., multiple doses; P/O ratio, ratio between predicted and observed value; Tmax, time to reach Cmax. AUC, area under the curve; CI, confidence interval; CL/F, apparent clearance; Cmax, peak concentration; m.d., multiple doses; P/O ratio, ratio between predicted and observed value; Tmax, time to reach Cmax. AUC, area under the curve; CI, confidence interval; CL/F, apparent clearance; Cmax, peak concentration; m.d., multiple doses; P/O ratio, ratio between predicted and observed value; Tmax, time to reach Cmax. AUC, area under the curve; CI, confidence interval; CL/F, apparent clearance; Cmax, peak concentration; m.d., multiple doses; P/O ratio, ratio between predicted and observed value; Tmax, time to reach Cmax. AUC, area under the curve; CI, confidence interval; CL/F, apparent clearance; Cmax, peak concentration; m.d., multiple doses; P/O ratio, ratio between predicted and observed value; Tmax, time to reach Cmax. AUC, area under the curve; CI, confidence interval; CL/F, apparent clearance; Cmax, peak concentration; m.d., multiple doses; P/O ratio, ratio between predicted and observed value; Tmax, time to reach Cmax. AUC, area under the curve; CI, confidence interval; CL/F, apparent clearance; Cmax, peak concentration; m.d., multiple doses; P/O ratio, ratio between predicted and observed value; Tmax, time to reach Cmax.
aUnless stated otherwise, observed pharmacokinetic (PK) parameters were obtained through Bayesian estimation by fitting the buprenorphine population PK model reported by Moore et al.46 to extracted concentration-time profiles. bAUC0–∞ and AUC0–τ for single and multiple dose studies, respectively. cValue as reported in the original study, i.e., not obtained through Bayesian estimation. dCalculated following CL/F = Dose/AUC0–∞. eGeometric mean of P/O ratios. aUnless stated otherwise, observed pharmacokinetic (PK) parameters were obtained through Bayesian estimation by fitting the buprenorphine population PK model reported by Moore et al.46 to extracted concentration-time profiles. bAUC0–∞ and AUC0–τ for single and multiple dose studies, respectively. cValue as reported in the original study, i.e., not obtained through Bayesian estimation. dCalculated following CL/F = Dose/AUC0–∞. eGeometric mean of P/O ratios. aUnless stated otherwise, observed pharmacokinetic (PK) parameters were obtained through Bayesian estimation by fitting the buprenorphine population PK model reported by Moore et al.46 to extracted concentration-time profiles. bAUC0–∞ and AUC0–τ for single and multiple dose studies, respectively. cValue as reported in the original study, i.e., not obtained through Bayesian estimation. dCalculated following CL/F = Dose/AUC0–∞. eGeometric mean of P/O ratios. aUnless stated otherwise, observed pharmacokinetic (PK) parameters were obtained through Bayesian estimation by fitting the buprenorphine population PK model reported by Moore et al.46 to extracted concentration-time profiles. bAUC0–∞ and AUC0–τ for single and multiple dose studies, respectively. cValue as reported in the original study, i.e., not obtained through Bayesian estimation. dCalculated following CL/F = Dose/AUC0–∞. eGeometric mean of P/O ratios. aUnless stated otherwise, observed pharmacokinetic (PK) parameters were obtained through Bayesian estimation by fitting the buprenorphine population PK model reported by Moore et al.46 to extracted concentration-time profiles. bAUC0–∞ and AUC0–τ for single and multiple dose studies, respectively. cValue as reported in the original study, i.e., not obtained through Bayesian estimation. dCalculated following CL/F = Dose/AUC0–∞. eGeometric mean of P/O ratios. aUnless stated otherwise, observed pharmacokinetic (PK) parameters were obtained through Bayesian estimation by fitting the buprenorphine population PK model reported by Moore et al.46 to extracted concentration-time profiles. bAUC0–∞ and AUC0–τ for single and multiple dose studies, respectively. cValue as reported in the original study, i.e., not obtained through Bayesian estimation. dCalculated following CL/F = Dose/AUC0–∞. eGeometric mean of P/O ratios. aUnless stated otherwise, observed pharmacokinetic (PK) parameters were obtained through Bayesian estimation by fitting the buprenorphine population PK model reported by Moore et al.46 to extracted concentration-time profiles. bAUC0–∞ and AUC0–τ for single and multiple dose studies, respectively. cValue as reported in the original study, i.e., not obtained through Bayesian estimation. dCalculated following CL/F = Dose/AUC0–∞. eGeometric mean of P/O ratios. aUnless stated otherwise, observed pharmacokinetic (PK) parameters were obtained through Bayesian estimation by fitting the buprenorphine population PK model reported by Moore et al.46 to extracted concentration-time profiles. bAUC0–∞ and AUC0–τ for single and multiple dose studies, respectively. cValue as reported in the original study, i.e., not obtained through Bayesian estimation. dCalculated following CL/F = Dose/AUC0–∞. eGeometric mean of P/O ratios. aUnless stated otherwise, observed pharmacokinetic (PK) parameters were obtained through Bayesian estimation by fitting the buprenorphine population PK model reported by Moore et al.46 to extracted concentration-time profiles. bAUC0–∞ and AUC0–τ for single and multiple dose studies, respectively. cValue as reported in the original study, i.e., not obtained through Bayesian estimation. dCalculated following CL/F = Dose/AUC0–∞. eGeometric mean of P/O ratios. aUnless stated otherwise, observed pharmacokinetic (PK) parameters were obtained through Bayesian estimation by fitting the buprenorphine population PK model reported by Moore et al.46 to extracted concentration-time profiles. bAUC0–∞ and AUC0–τ for single and multiple dose studies, respectively. cValue as reported in the original study, i.e., not obtained through Bayesian estimation. dCalculated following CL/F = Dose/AUC0–∞. eGeometric mean of P/O ratios. aUnless stated otherwise, observed pharmacokinetic (PK) parameters were obtained through Bayesian estimation by fitting the buprenorphine population PK model reported by Moore et al.46 to extracted concentration-time profiles. bAUC0–∞ and AUC0–τ for single and multiple dose studies, respectively. cValue as reported in the original study, i.e., not obtained through Bayesian estimation. dCalculated following CL/F = Dose/AUC0–∞. eGeometric mean of P/O ratios.