Bioequivalence and Bioavailability Forum

Dear All Forum Members,

Does somebody have an experience of conducting pharmacokinetic study of in Liposomal Amphotericin B injection in healthy adult human subjects? As per SPC the dose of the infusion should be 3 mg/kg body weight and the desired dilution is 0.2 mg/ml to 2mg/ml. So for the subject having weight 70, total dose= 70 kg * 3 mg/kg =210 mg; whereas for subject have weight 60; total dose= 55 kg* 3mg/kg=165 mg.

Now as per SPC the reconstituted concentration should be in the range of 0.2 mg/ml to 2mg/ml; therefore the volume of dose would be different for different subject for e.g it would be 105 ml and 82.5 ml (2mg/ml reconstituted solution) for 70 and 55 kg of body weight of subject.

But, the time of infusion is constant for all subjects; which is over a period of 2 hrs, considering this the flow of infusion is required to be optimized to ensure it will last for 2 hrs. Now my question is whether different flow of infusion for different subject will have an impact on the PK? And if yes, how it should be dealt with?

Shall we have a uniform final volume (may be 500/ 250 ml) keeping the dose 3mg/kg in mind so that flow of infusion can be kept same for all subjects? Or it does not matter what is the final volume of the infusion?

Also how to take care of infusion period which might be slightly different for every subject (even for same subject in different period) may differ by 5-10 min?

Thanking you in advance for your valuable comments and suggestions.

Regards,

Ratnakar