Buccal acetaminophen provides fast analgesia: two randomized clinical trials in healthy volunteers

Figures & data

Figure 1 Chronology of clinical trials 1 and 2, indicating assessment of pain thresholds (*), elapsed times, drug administration, and blood samplings (♦), and blood samplings only for clinical trial 2.

Abbreviations: T, time; h, hour.

Table 1 Clinical trial 1: descriptive statistics on pharmacokinetic parameters

Treatment	Tmax (min)	Cmax (μg/mL)	AUClast (μg · min/mL)	Cmax/dose (μg/mL/mg)	AUC last/dose (μg · min/mL/mg)
ivAPAP (1,000 mg)
Mean	12.00	15.51	994.77	0.0155	0.9948
SD	5.28	3.03	147.86	0.0030	0.1479
CV	43.98	19.55	14.86	19.5473	14.8634
Median	10.00	13.90	1,011.85	0.0139	1.0119
bAPAP (250 mg)
Mean	46.00	2.16	166.73	0.0086	0.6669
SD	26.67	0.90	70.65	0.0036	0.2826
CV	57.98	41.59	42.37	41.5858	42.3719
Median	40.00	1.90	147.90	0.0076	0.5916

Abbreviations: APAP, acetaminophen; AUC, area under the curve; b, buccal; C_max, peak concentration; CV, coefficent of variation; iv, intravenous; min, minute; SD, standard deviation; T_max, time to maximum plasma concentration.

Table 2 Clinical trials 1 (CT1) and 2 (CT2): descriptive statistics on pharmacodynamic-derived parameters (pain thresholds)

	Emax (g)	AUC (g · min)
CT1 (250 mg)
bAPAP
Mean	59	1,827
SD	55	3,697
CV	93	202
ivAPAP
Mean	37	659
SD	40	3,599
CV	110	546
CT2 (125 mg)
bAPAP
Mean	48	1,968
SD	25	2,306
CV	52	117
ivAPAP
Mean	37	1,111
SD	25	2,106
CV	69	189
sAPAP
Mean	39	1,203
SD	48	2,137
CV	25	178

Abbreviations: APAP, acetaminophen; AUC, area under the curve; b, buccal; CV, coefficent of variation; E_max, maximum of action observed; iv, intravenous; min, minute; s, sublingual; SD, standard deviation.

Figure 2 Pharmacokinetic profile of 1 g intravenous (iv) and 250 mg buccal acetaminophen.

Figure 3 Antinociceptive profiles obtained during (A) clinical trial 1 for 1 g intravenous (iv) and 250 mg buccal (b) acetaminophen (APAP) and (B) during clinical trial 2 for 1 g iv APAP, 125 mg bAPAP, and 125 mg sublingual (s)APAP.

Notes: **P<0.01 (bAPAP versus ivAPAP); ^Δ P<0.05; ^ΔΔ P<0.01 (bAPAP versus sAPAP).
Abbreviation: PT, pain threshold.