Table 3. Predicted and observeda buprenorphine pharmacokinetic parameters following administration of sublingual tablets
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)
McAleer et al.52 2 sublingual, tablet 27 0.0 (19–42) Predicted 7.32 273.1 1.37 1.14
Observed 10.3 195.1 1.47 1.48
P/O ratio 0.71 1.40 0.93 0.77
Ciraulo et al.29 4 sublingual, tablet 23 30.4 34.5 Predicted 15.9 252.2 2.67 1.12
Observed 9.62 415.7 1.87 1.00
P/O ratio 1.65 0.61 1.43 1.12
Jönsson et al.53 4 sublingual, tablet 61 41.0 31.4 (19–54) Predicted 13.7 291.5 2.31 1.08
Observed 21.8 183.7 2.14 1.69
P/O ratio 0.63 1.59 1.08 0.64
Nath et al.27 8 sublingual, tablet 6 0.0 28 (23–42) Predicted 22.6 353.3 3.52 1.15
Observed 23.5 340.5 2.95 1.10
P/O ratio 0.96 1.04 1.19 1.05
McAleer et al.52 8 sublingual, tablet 27 0.0 (19–42) Predicted 22.9 350.0 3.49 1.14
Observed 29.1 275.3 3.84 1.27
P/O ratio 0.79 1.27 0.91 0.90
Ciraulo et al.29 8 sublingual, tablet 23 30.4 34.5 Predicted 27.1 295.0 4.15 1.12
Observed 20.8 384.5 2.47 0.99
P/O ratio 1.30 0.77 1.68 1.13
McAleer et al.52 12 sublingual, tablet 27 0.0 (19–40) Predicted 31.0 387.4 4.35 1.15
Observed 41.0 292.7 4.81 1.12
P/O ratio 0.76 1.32 0.90 1.03
McAleer et al.52 16 sublingual, tablet 27 0.0 (19–40) Predicted 38.2 418.7 4.98 1.15
Observed 52.7 303.4 6.11 0.79
P/O ratio 0.72 1.38 0.82 1.46
Chawarski et al.25 16 sublingual, tablet, m.d. 18 29.5 37.8 Predicted 45.5 379.0 6.68 1.12
Observed 31.2 512.6 3.45 0.71
P/O ratio 1.46 0.74 1.94 1.58
Ciraulo et al.29 16 sublingual, tablet 23 30.4 34.5 Predicted 45.0 355.2 5.93 1.12
Observed 42.0 381.0 4.11 0.96
P/O ratio 1.07 0.93 1.44 1.17
Moody et al.54 16 sublingual, tablet, m.d. 11 100.0 41.5 Predicted 46.8 378.2 6.87 1.00
Observed 57.8 276.7 6.58 0.90
P/O ratio 0.81 1.37 1.04 1.11
Moody et al.54 16 sublingual, tablet, m.d. 20 0.0 35.7 Predicted 45.3 388.3 6.58 1.17
Observed 40.9 390.8 4.54 1.05
P/O ratio 1.11 0.99 1.45 1.11
Jönsson et al.53 16 sublingual, tablet 64 40.6 32.1 (20–51) Predicted 39.7 403.4 5.17 1.09
Observed 56.3 284.1 5.29 1.54
P/O ratio 0.71 1.42 0.98 0.71
Chawarski et al.25 24 sublingual, tablet, m.d. 19 29.5 37.8 Predicted 60.1 431.0 8.01 1.13
Observed 56.8 422.2 6.86 0.91
P/O ratio 1.06 1.02 1.17 1.24
Ciraulo et al.29 24 sublingual, tablet 23 30.4 34.5 Predicted 59.5 403.5 6.81 1.13
Observed 61.7 389.1 5.08 0.75
P/O ratio 0.96 1.04 1.34 1.51
Chawarski et al.25 32 sublingual, tablet, m.d. 20 29.5 37.8 Predicted 72.2 473.8 8.76 1.13
Observed 55.5 576.1 6.17 0.97
P/O ratio 1.30 0.82 1.42 1.16
Geo. meanc 0.96 1.07 1.20 1.07
(95% CI) (0.82–1.12) (0.92–1.24) (1.05–1.37) (0.94–1.23)
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.
aObserved 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. cGeometric mean of P/O ratios. aObserved 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. cGeometric mean of P/O ratios. aObserved 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. cGeometric mean of P/O ratios. aObserved 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. cGeometric mean of P/O ratios. aObserved 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. cGeometric mean of P/O ratios. aObserved 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. cGeometric mean of P/O ratios. aObserved 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. cGeometric mean of P/O ratios. aObserved 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. cGeometric mean of P/O ratios. aObserved 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. cGeometric mean of P/O ratios. aObserved 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. cGeometric mean of P/O ratios. aObserved 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. cGeometric mean of P/O ratios.