The pharmacokinetic interaction between alfentanil and propofol in healthy male volunteers

M.J. Mertens, J. Vuyk, E. Olofsen, A.G.L. Burm, J.G. Bovill, Department of Anaesthesiology, Leiden University Medical Center, The Netherlands

Background & goal of the study

The pharmacodynamic interaction between alfentanil (ALF) and propofol (PROP) has been described in detail. In contrast, very little is known on wether PROP also affects the pharmacokinetics of ALF. We studied the effect of a semi-steady-state concentration of PROP on the distribution and elimination of ALF.

Material and methods

With ethics committee approval and informed consent the pharmacokinetics of alfentanil were studied in 8 healthy male volunteers in the absence and presence of propofol in a randomized cross-over manner. While breathing 40% O₂ in air, ALF 12.5 mg/kg, iv, was administered in 2 min, followed by 25 mg/kg/h for 58 min (session A). With an interval of 3 weeks, the same ALF infusion scheme was given in the presence of a target controlled infusion of PROP¹ at a constant target PROP concentration of 1.5 mg/ml that was started 15 min before and maintained up to 6 h after termination of the ALF infusion (session B). The ECG, BP, RR, ET-CO₂ and SaO₂ were monitered continuously. The ET-CO₂ was maintained below 45 mmHg. Venous blood samples for ALF and PROP determination were taken frequently during and up to 6 h after termination of the ALF infusion. The pharmacokinetics of alfentanil were determined using the software package WINNONLIN and compared between sessions A and B using the paired t-test.

Results and discussion

The mean age and weight (± SD) of the volunteers were 24 ± 3 yr and 74 ± 6 kg. The data was best fitted with a 2 compartment pharmacokinetic model. Lag time was included in the model because of venous sampling.

Conclusion

Propofol alters the pharmacokinetics of alfentanil, mainly during the initial distribution. These differences might be explained by the difference in the haemodynamic parameters in session A and B.

References

1. Anesth Analg 1987;66:12-1263

Table 1: The pharmacokinetic parameters of alfentanil and the heamodynamic parameters in the absence (session A) and in the presence (session B) of propofol

	Session A	Session B	Difference (%)	P value
V1 (ml/kg)	191 ± 95	76 ± 23	-60	0.01
Vss (ml/kg)	393 ± 81	42 ± 15	-89	0.18
Cl (ml/kg/min)	4.8 ± 1.5	3.9 ± 1.0	-19	0.07
Cld (ml/kg/min)	9.4 ± 5.9	22.3 ± 24.9	137	0.19
t½ alpha	7.9 ± 4.8	2.2 ± 0.8	-72	0.01
t½ beta	70 ± 9	74 ± 14	6	0.03
lag time (s)	109 ± 14	32 ± 35	-71	0.002
Cl (l/m^2)	3.28 ± 0.37	3.13 ± 0.38	-5	0.28
MAP (mmHg)	81 ± 6	69 ± 5	-15	0.01
SVR (dynes/s/m^-5)	1008 ± 107	908 ± 109	-10	0.05