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Dear PK Group,
How should I approach the modelling of a subcutaneous bolus injection
which will be administered shortly (about 10mins) after a continuous
(24hour) subcut infusion of the drug has been stopped? The half life of
the drug is about 40mins.
I've come across examples of modelling a bolus loading dose with an
infusion, but I need some advice on this particular scenario.
Thanks very much.
Wendy Ingram
Research Student
Pharmaceutical and Biomedical Research Group
Dept of Pharmacy
Derriford Hospital
Plymouth
Devon
PL6 8DH
UK
Tel: +44 (0)1752 763414
Fax: +44 (0)1752 763418
email: wendy.ingram.at.phnt.swest.nhs.uk
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Hello Wendy,
I think you could model this as Bolus followed by a continuous
infusion in the classic intravenous one compartment sense:
[X/Vd]e-kt + [Ko/KVd][1-ekt]
However, if the drug does not undergo rapid absorption, then the bolus
might best be modeled as first order absorption:
[KaFD/(Ka-Ke)Vd*][e-ket - e-kat] + [Ko/KVd][1-e-ket]
*(don't forget the Vd in the first order absorption equation denominator)
This is assuming that the rate limiting factor in the subcutaneous infusion
is the rate of infusion itself. If this is not the case, then the process could
be modeled as two separate first order absorption processes, with the
infusion being
modeled with a slower Ka(2), reflecting the slower absorption of the continuous
infusion. The continuous infusion would then be modeled as would the
first order
absorption of an orally administered sustained release product.
[Ka(1)FD/(Ka(1)-Ke)Vd][e-ket - e-ka(1)t] + [Ka(2)FD/(Ka(2)-Ke)Vd][e-ket -
e-ka(2)t]
These equations also assume a one compartment model, which is probably
a good choice when dealing with a first order absorption process which tends
to minimize the appearance of a distribution phase in the plasma
concentration curve.
Bonne chance!!
Mike Leibold, PharmD, RPh
ML11439.-a-.goodnet.com
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