madman
Super Moderator
Context
Can injectable testosterone undecanoate (TU) be administered effectively and acceptably by the subcutaneous route?
Objective
To investigate the acceptability and pharmacokinetics (PK) of sc injection of TU.
Design
Randomized sequence, cross-over clinical study of sc vs im TU injections.
Setting
Ambulatory clinic of an academic Andrology centre.
Participants
Twenty men (11 hypogonadal, 9 transmen) who were long-term users of TU injections.
Intervention
Injection of 1000 mg TU (in 4 ml castor oil vehicle) by sc or im route.
Main Outcome Measures
Patient reported Pain, Acceptability and Preference scales. PK by measurement of serum testosterone, dihydrotestosterone (DHT) and estradiol (E2) concentrations with application of population PK methods and dried blood spot (DBS) sampling.
Results
Pain was greater after sc compared with im injection 24 hour (but not immediately) after injection but both routes were equally acceptable. Ultimately 11 preferred im, 6 preferred sc and 3 had no preference. The DBS-based PK analysis of serum testosterone revealed a later time of peak testosterone concentration after sc vs im injection (8.0 vs 3.3 days) but no significant route differences in model-predicted peak testosterone concentration (8.4 vs 9.6 ng/ml) or mean resident time (183 vs 110 days). The PK of venous serum testosterone, DHT and E2 did not differ according to route of injection.
Conclusions
We conclude that sc TU injection is acceptable but produces greater pain 24 hours after injection which may contribute to the overall majority preference for the im injection. The PK of testosterone, DHT or E2 did not differ substantially between sc and im routes. Hence while further studies are required, the sc route represents an alternative to im injections without a need to change dose for men where im injection is not desired or recommended.
We conclude that with clinic-based delivery sc injection of TU is effective with similar PK parameters to im TU so not requiring dose modification. It is acceptable but generally less preferable compared with im TU for men. Thereby sc TU injection constitutes an alternative delivery route in circumstances where im injection is not desired, feasible or recommended. Despite causing slightly more injection site pain 24 hours after injection, sc injection was generally acceptable but not preferred over im injection by most participants in this study who were long-term satisfied users of im TU. These preliminary findings indicate that sc injection may prove a viable alternative delivery route where required. Whether self-injection of either the 4ml or two 2ml injections is feasible or acceptable remains to be determined.
Can injectable testosterone undecanoate (TU) be administered effectively and acceptably by the subcutaneous route?
Objective
To investigate the acceptability and pharmacokinetics (PK) of sc injection of TU.
Design
Randomized sequence, cross-over clinical study of sc vs im TU injections.
Setting
Ambulatory clinic of an academic Andrology centre.
Participants
Twenty men (11 hypogonadal, 9 transmen) who were long-term users of TU injections.
Intervention
Injection of 1000 mg TU (in 4 ml castor oil vehicle) by sc or im route.
Main Outcome Measures
Patient reported Pain, Acceptability and Preference scales. PK by measurement of serum testosterone, dihydrotestosterone (DHT) and estradiol (E2) concentrations with application of population PK methods and dried blood spot (DBS) sampling.
Results
Pain was greater after sc compared with im injection 24 hour (but not immediately) after injection but both routes were equally acceptable. Ultimately 11 preferred im, 6 preferred sc and 3 had no preference. The DBS-based PK analysis of serum testosterone revealed a later time of peak testosterone concentration after sc vs im injection (8.0 vs 3.3 days) but no significant route differences in model-predicted peak testosterone concentration (8.4 vs 9.6 ng/ml) or mean resident time (183 vs 110 days). The PK of venous serum testosterone, DHT and E2 did not differ according to route of injection.
Conclusions
We conclude that sc TU injection is acceptable but produces greater pain 24 hours after injection which may contribute to the overall majority preference for the im injection. The PK of testosterone, DHT or E2 did not differ substantially between sc and im routes. Hence while further studies are required, the sc route represents an alternative to im injections without a need to change dose for men where im injection is not desired or recommended.
We conclude that with clinic-based delivery sc injection of TU is effective with similar PK parameters to im TU so not requiring dose modification. It is acceptable but generally less preferable compared with im TU for men. Thereby sc TU injection constitutes an alternative delivery route in circumstances where im injection is not desired, feasible or recommended. Despite causing slightly more injection site pain 24 hours after injection, sc injection was generally acceptable but not preferred over im injection by most participants in this study who were long-term satisfied users of im TU. These preliminary findings indicate that sc injection may prove a viable alternative delivery route where required. Whether self-injection of either the 4ml or two 2ml injections is feasible or acceptable remains to be determined.
