- On 13 Sep 1999 at 14:10:56, Chantal Le guellec (leguellec.-at-.med.univ-tours.fr) sent the message

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Dear all,

I would appreciate any comment on the following:

Let's consider a drug with two-compartmental pharmacokinetics

administered by IV infusion. Distribution occurs as soon as the infusion

has started and goes on during all the infusion period.

Can the distribution phase be masked by a prolonged infusion? In what

particular cases?

A very practical example: the distribution phase of vancomycin is of

about 2-3 hours. Shall we consider that distribution is accomplished 2-3

h after the end or after the beginning of the infusion?

Many thanks for any advice. - On 13 Sep 1999 at 21:43:01, David_Bourne (david.-at-.boomer.org) sent the message

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[Three replies - db]

Date: Tue, 14 Sep 1999 09:07:12 +1200

From: Nick Holford

X-Accept-Language: en

To: PharmPK.at.boomer.org

Subject: Re: PharmPK Distribution phase

Distribution (and elimination) are occurring all the time. There is no

"end" to the distribution of the drug.

I think you may be asking for some more practical advice however e.g. at

what time after a 3 h infusion could one draw a blood sample for TDM and

be able to assume one compartment kinetics?

Is this what you want to know?

--

Nick Holford, Dept Pharmacology & Clinical Pharmacology

University of Auckland, Private Bag 92019, Auckland, New Zealand

email:n.holford.-a-.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556

http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm

---

Date: Mon, 13 Sep 1999 15:46:39 -0700

From: "David Nix, Pharm D."

Organization: College of Pharmacy

To: PharmPK.aaa.boomer.org

Subject: Re: PharmPK Distribution phase

This problem can be simplified by considering an infusion to be multiple

bolus doses. If the infusion is 100 mg over 50 minutes, then this would

be similar to giving a 2 mg bolus every minute. Suppose that the

distribution half life is 10 minutes. Distribution for drug given

during the first 10 minutes would be nearly complete by the end of the

infusion. However, distribution of drug given within the last few

minutes of the infusion would be just starting. Whether the

distribution phase is masked by the infusion will depend how prominent

the distribution is after a bolus dose and how many "2 mg bolus doses"

are still undergoing distribution (this is based on distribution

half-life).

For a two compartment model where C(t)=A*exp(-alpha*t)+B*exp(-beta*t), a

large A coefficient compared to B coefficient would be associated with a

prominent distribution phase. The superposition principle will apply to

the repeated small "bolus doses".

---

From: =?ks_c_5601-1987?B?ueix1by3?=

To:

Subject: Re: PharmPK Distribution phase

Date: Tue, 14 Sep 1999 09:01:42 +0900

X-Priority: 3

Dear, all

It will be helpful to see Fig 2.10 and relevant text at page 71 of

Gibaldi & Perrier, Pharmacokinetics, 2nd ed. revised and expanded.

Marcel Dekker, 1982

Kyun-Seop Bae MD

Department of Pharmacology

Seoul National University College of Medicine

&

Clinical Pharmacolgy Unit

Seoul National University Hospital - On 14 Sep 1999 at 22:02:56, "Stephen Duffull" (sduffull.at.fs1.pa.man.ac.uk) sent the message

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Just to clarify David's last comment

It is not just the large A coefficient that is important it

is how large A/alpha is compared to B/beta.

Regards

Steve

=====================

Stephen Duffull

School of Pharmacy

University of Manchester

Manchester, M13 9PL, UK

Ph +44 161 275 2355

Fax +44 161 275 2396

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