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When a drug is given intraperitoneally, how is it absorbed? Where
does the drug go to?
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[Two replies - db]
Date: Tue, 18 Apr 2000 02:02:05 -0700 (MST)
X-Sender: ml11439.-a-.pop.goodnet.com
To: PharmPK.-a-.boomer.org
From: ml11439.-a-.goodnet.com (Michael J. Leibold)
Subject: Re: PharmPK
Discussion group,
When a drug is administered into the peritoneum, it is usually
placed in a pertioneal dialysis solution. Studies concerning the
influence of antibiotics from the peritoneal cavity have found that
the following factors influence the absorption of drugs from the
peritoneal cavity(1):
1)antibiotic concentration in the dialysate
2) Duration of drug administration
3) drug-protein binding in dialysate
4) presence or absence of peritonitis
5) plasma and extravascular protein binding
6) volume of distribution
7) nonrenal clearance mechanisms
The following theoretical compartment model has been proposed(1);
IP dose> Peritoneal cavity-----> Vascular space---> Extravascular space
DrugPB<-> Drug Free--> Drug PB<-->Drug Free--> Drug PB<--Drug free
\>Clearance \>Clearance
When administered IP, the free drug is able to diffuse across the
peritoneal membrate into the circulation, where is can be elmininated
or distributed to the extravascular space. In the extravascular space,
the drug may be eliminated by nonrenal mechanisms. (1) As the drug
concentration in the dialysate and dwell time increase, the extent of
peritoneal absorption increases. Peritoneal protein binding increases in
peritonitis, but the permeability of the peritoneal membrane increases
resulting in increased absorption during peritonitis.(1) The fraction
absorbed also depends one the physiochemical properties of the antibiotic
itself, with F values ranging from .52 for vancomycin to 0.86 for moxalactam,
which increase to .91 and .94 (respectively) during peritonitis.(1)
The peritoneal cavity is lined by a semi-permeable membrane accross
which dialysis or diffusion occurs. The blood vessels supplying and
draining the abdominal viscera, musculature and messentery, constitute
a blood filled compartment into which drugs can diffuse from the peritoneum.(2)
This would include the hepatic portal system as well as other veins and
arteries supplying the region.
Mike Leibold, PharmD, RPh
ML11439.at.goodnet.com
References
1)Morse, G.D., Apicella, M.A., Walshe, J.J., Absorption of intraperitoneal
antibiotics, DICP 1988;22:58-61
2) DiPiro, J.T., et al.,Pharmacotherapy, A Pathophysicological Approach 3rd
ed., New Jersey, Appleton& Lange 1997;991-1001
---
From: "Raj"
To:,
"Multiple recipients of PharmPK - Sent by"
Subject: Re: PharmPK Intraperitoneal absorption of drugs
Date: Tue, 18 Apr 2000 08:19:14 -0400
X-Priority: 3
Drugs by IP route enter systemic circulation through the portal vein and
hence behave for all practical purposes, like oral route of administration.
However, the surface area for absorption is quite large and hence, one may
not see the absorption phase if the sampling is not done at frequent
intervals. You may want to look at two articles
1. Canal et al. A pharmacokinetic model for intraperitoneal administration
of drugs: application to teniposide in humans. J Pharm Sci, 78: 389-392
(1989)
2. Lucas et al. The route of absorption of intraperitoneally administered
compounds. J Pharmacol Exp Ther. 178: 562-568 (1971).
Good Luck,
Raj
N.V. Nagaraja, PhD,
Post Doc Res Assoc,
Department of Pharmaceutics,
University of Florida,
Gainesville, FL-32610
Ph: 352-846-3257
Fax: 352-392-4447
E-mail: nagaraja.-at-.ufl.edu
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The peritoneal membrane is a semipermeable membrane, lined with a
capillary bed. Fluid and solutes can be removed from the blood across
this membrane, as in peritoneal dialysis. In general, when drugs are
administered into the peritoneal cavity, absorption may occur through
the membrane, into the capillaries and the systemic circulation.
Factors that must be considered include physicochemical properties of
the drug, integrity of the membrane, and blood flow to peritoneum.
Hope this helps,
Tom
----
Thomas C. Dowling, PharmD, PhD
Assistant Professor
Department of Pharmacy Practice and Science
Pharmacokinetics and Biopharmaceutics Laboratory
UMAB
100 N. Penn St., Rm. 540D
Baltimore, MD 21201
410.706.0884 phone
410.706.6580 fax
410.492.9888 page
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