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ALFENTANIL (RAPIFEN*): ANIMAL PHARMACOLOGY AND CLINICAL USE
180.
ALFENTANIL (RAPIFEN*): ANIMAL PHARMACOLOGY AND CLINICAL USE
R.F.
Cookson
Janssen Pharmaceutical Ltd. Grove, Wantage. Alfentanil is a short acting intravenous narcotic analgesic supplement for use during anaesthesia. Developed by Janssen (Cookson Niemegeers and Vanden Bussche 1983) as a fentanyl analogue with properties more appropriate for short operative procedures, it was introduced into clinical use in the United Kingdom in September 1983. Relatively little information is available on the effects of alfentanil in large animals apart from man, but a great deal of work has been done in small animals such as rats, mice, rabbits and dogs. Much of this work was performed during the normal pre-clinical development of a drug for human use and detailed reports are available upon request (Janssen Pharmaceutical Ltd.. data on file).
Figure 1
illustrates the relative time course of effect of fentanyl, alfentanil, morphine and pethidine in the rat. At 16 times the lowest ED50 the "duration of action" of alfentanil, fentanyl and morphine are 36, 120 and 300 minutes respectively. Pleuvry and her colleagues in Manchester have compared in some detail the respiratory depressant affects of alfentanil and fentanyl in spontaneously breathing rabbits (Brown, Pleuvry and Kay 1980, Brown and Pleuvry 1981).
The short duration of action o f alfentanil was
confined in this species. Both drugs produce a rapid decrease in minute volume and respiratory frequency which is more rapidly reversed for alfentanil. Repeat injections of alfentanil every 10 minutes produce a distinctive and regular decrease in respiratory rate, similar after each injection, In contrast, fentanyl when given at an Trademark.
181.
equidepressant dose provokes a tumuiative decrease,. even when injected at intervals of 15 minutes.
Other work by these authors has denonstrated
that the respiratory effects of alfentanil are snore easily reversed by naloxline than are the respiratcry effects of ientanyl. StGdies in anaesthetfsed inongel dogs have shown that cumulative doses of alfentanil of :60~gikg to 5mg/kg were followed by remarkable cardiovascular stability. Even the negative inotropic effect o f a massive bolus of 5 ng/kg was not seen when the drug was infused over 50 minutes.
The short action and marked cardiovascular safety of alfentanil have resulted in its clinical use over a wide dose range.
In short
operations, spontaneous respiration may be maintained by slow injection of 5
- 10 ug/kg.
Higher doses require assisted ventilation but last
for shorter periods than equipotent doses of fentanyl. Providing a suitable loading dose is given, infusions of alfentanil in ventilated patients may represent the most logical way to give this short acting opioid.
The clinical versatility of the agent is discussed elsewhere
(Cookson et a1 1983).
182.
REFERENCES
Br0wn.J.H. Brown,J.H.,
and Pleuvry,B.J. Pleuvry,B.J.
(1981).
6r.J.
and Kay,B. (1980).
Cookson,R.F., Nienegeers,C.J.E. Br. J. Anaesth. 55, 1475.
Anaesth. 6r.J.
53, 1033. Anaesth.
52,
and Vanden Bussche,G. (1983).
1101.
183.
t
1 1.811
3.75
7.50
15
30
€0 120
240360 480
Time after i.v. inlemon (mid
FIGURE 1
Effect of time a f t e r injection on ED,-* values in rat t a i l withdrawal test (reproduced from Cookson e t a l , with permission).
ALFENTANIL (RAPIFEN*): ANIMAL PHARMACOLOGY AND CLINICAL USE
R.F.
Cookson
Janssen Pharmaceutical Ltd. Grove, Wantage. Alfentanil is a short acting intravenous narcotic analgesic supplement for use during anaesthesia. Developed by Janssen (Cookson Niemegeers and Vanden Bussche 1983) as a fentanyl analogue with properties more appropriate for short operative procedures, it was introduced into clinical use in the United Kingdom in September 1983. Relatively little information is available on the effects of alfentanil in large animals apart from man, but a great deal of work has been done in small animals such as rats, mice, rabbits and dogs. Much of this work was performed during the normal pre-clinical development of a drug for human use and detailed reports are available upon request (Janssen Pharmaceutical Ltd.. data on file).
Figure 1
illustrates the relative time course of effect of fentanyl, alfentanil, morphine and pethidine in the rat. At 16 times the lowest ED50 the "duration of action" of alfentanil, fentanyl and morphine are 36, 120 and 300 minutes respectively. Pleuvry and her colleagues in Manchester have compared in some detail the respiratory depressant affects of alfentanil and fentanyl in spontaneously breathing rabbits (Brown, Pleuvry and Kay 1980, Brown and Pleuvry 1981).
The short duration of action o f alfentanil was
confined in this species. Both drugs produce a rapid decrease in minute volume and respiratory frequency which is more rapidly reversed for alfentanil. Repeat injections of alfentanil every 10 minutes produce a distinctive and regular decrease in respiratory rate, similar after each injection, In contrast, fentanyl when given at an Trademark.
181.
equidepressant dose provokes a tumuiative decrease,. even when injected at intervals of 15 minutes.
Other work by these authors has denonstrated
that the respiratory effects of alfentanil are snore easily reversed by naloxline than are the respiratcry effects of ientanyl. StGdies in anaesthetfsed inongel dogs have shown that cumulative doses of alfentanil of :60~gikg to 5mg/kg were followed by remarkable cardiovascular stability. Even the negative inotropic effect o f a massive bolus of 5 ng/kg was not seen when the drug was infused over 50 minutes.
The short action and marked cardiovascular safety of alfentanil have resulted in its clinical use over a wide dose range.
In short
operations, spontaneous respiration may be maintained by slow injection of 5
- 10 ug/kg.
Higher doses require assisted ventilation but last
for shorter periods than equipotent doses of fentanyl. Providing a suitable loading dose is given, infusions of alfentanil in ventilated patients may represent the most logical way to give this short acting opioid.
The clinical versatility of the agent is discussed elsewhere
(Cookson et a1 1983).
182.
REFERENCES
Br0wn.J.H. Brown,J.H.,
and Pleuvry,B.J. Pleuvry,B.J.
(1981).
6r.J.
and Kay,B. (1980).
Cookson,R.F., Nienegeers,C.J.E. Br. J. Anaesth. 55, 1475.
Anaesth. 6r.J.
53, 1033. Anaesth.
52,
and Vanden Bussche,G. (1983).
1101.
183.
t
1 1.811
3.75
7.50
15
30
€0 120
240360 480
Time after i.v. inlemon (mid
FIGURE 1
Effect of time a f t e r injection on ED,-* values in rat t a i l withdrawal test (reproduced from Cookson e t a l , with permission).