- On 6 Aug 1999 at 11:50:52, "INGRAM Wendy, Pharmacy" (wendy.ingram.at.phnt.swest.nhs.uk) sent the message

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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 - On 9 Aug 1999 at 22:03:06, ml11439.-a-.goodnet.com (Michael J. Leibold) sent the message

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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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