Table 2.

Effect of reducing the dose of propranolol and/or inserting a delay between propranolol and rizatriptan administration on pharmacokinetic parameters for rizatriptan in 12 healthy subjects

	Rizatriptan pharmacokinetic parameters (arithmetic means±s.d.) (n = 12)
Parameter	10 mg rizatriptan+ placebo propranolol	10 mg Rizatriptan+ 60 mg propranolol	10 mg rizatriptan 1 h after 60 mg propranolol	10 mg rizatriptan 1 h after 120 mg propranolol	10 mg rizatriptan 2 h after 120 mg propranolol
AUC(0,∞) (ng ml−1 h)	61.8 ± 12.1	80.9 ± 16.6	84.7 ± 27.8	89.3 ± 21.9	86.3 ± 22.9
Geometric mean AUC ratio		1.38*	1.42*	1.53*	1.45*
vs rizatriptan alone		(1.24, 1.54)	(1.27, 1.58)	(1.37, 1.71)	(1.30, 1.61)
(97.5% confidence interval)
Cmax (ng ml−1)	19.5 ± 4.8	25.0 ± 4.8	27.1 ± 9.9	24.8 ± 7.9	27.2 ± 10.1
Geometric mean Cmax ratio vs		1.39*	1.48*	1.29*	1.45*
rizatriptan alone		(1.21, 1.60)	(1.29, 1.70)	(1.12, 1.49)	(1.26, 1.67)
(90% confidence interval)
tmax (h)	0.9 ± 0.5	0.8 ± 0.4	1.2 ± 0.4	1.2 ± 0.7	1.3 ± 0.7
Kela	0.379	0.361	0.379	0.363	0.337
	(0.335, 0.423)	(0.317, 0.405)	(0.335, 0.423)	(0.319, 0.407)	(0.293, 0.381)
t½ (h)b	1.9	2.0	1.7	2.0	1.9
Ue (%)	9.7 ± 3.0	11.5 ± 3.2	11.0 ± 4.0	14.8 ± 4.8	10.6 ± 3.3
CLR (ml min−1)	261.5 ± 64.6	242.8 ± 72.8	227.4 ± 85.9	294.3 ± 119.4	229.9 ± 134.8

^*P < 0.01 vs 10 mg rizatriptan+propranolol placebo.

^aArithmetic mean (95% confidence interval).

^bHarmonic mean.

AUC(0,∞)=area under the concentration-time curve from 0 to infinity; C_max=maximal plasma concentration; t_max=time to achieve maximal plasma concentration; K_el=elimination rate constant; CL_R=renal clearance.