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The following message was posted to: PharmPK
Hi:
Quick question: How do we explain bioavailability of greater than 100%
(125%) without evidence of enterohepatic recirculation?
Thanks
Vuong
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The following message was posted to: PharmPK
I don't know anything about your drug, but I believe chloramphenicol's
bioavailability is greater than 100% because the parenteral form has to
be
released from succinate. Perhaps your drug in its IV form is a prodrug.
Michael Neely, MD
Assistant Professor of Pediatrics
Division of Pediatric Infectious Diseases
Laboratory of Applied Pharmacokinetics
Keck School of Medicine
University of Southern California
1640 Marengo St., Suite 300
Los Angeles, CA 90033
Tel: (323) 226-5068
Fax: (323) 226-8362
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The following message was posted to: PharmPK
Hi Vuong,
Primary assumption for comparing bioavailabilities is that clearance
remains constant, that is, clearance is independent of the route of
administration. Either factor that influence k or V (CL = k.V) can
result in such findings. For instance, this can be expected for drugs
that have cardiovascular properties. Drug perfusion/blood flows/cardiac
output may vary with the route of administration.
Another explanation may be that when you give your drug as an iv bolus
or short infusion you do not have enough sampling times in the upswing
of the curve. As a result you may underestimate the AUC after the IV
administration.
Best regards,
Kees
Kees Bol, PhD
Director Clinical Pharmacokinetics
Kinesis Holding
Consultants in drug development
Lage Mosten 29
4822 NK Breda
The Netherlands
tel: +31 (0) 76 54 80 621
gsm: +31 (0) 65 31 26 153
fax: +31 (0) 76 54 21 777
kees.bol.aaa.kinesis-pharma.com
www.kinesis-pharma.com
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Erroneous estimation of bioavailability is possible when
within-individual variability is present in the serum clearance of the
drug.
A reference about this problem is the following:
J. M. Lanao, M. T. Vicente, M. L. Sayalero and A. Domínguez-Gil
A method for the calculation of bioavailability in slow release
formulations in the presence of within-individual variability.
Int. J. Pharm. 86: 123-130. 1992.
Regards.
J.M. Lanao
Dpt. Pharmacy and Pharmaceutical Technology
Faculty of Pharmacy
University of Salamanca
Spain
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Hi!
The good Dr. Neely is correct. The "other thing" is that, since the
succinate is water soluble, there is excellent renal clearance. A
relatively large percentage is recovered in the urine before being
cleaved to Chloro.
George Drusano
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The following message was posted to: PharmPK
Did you use the same size of dosage in iv and oral administration?
Cause if
you used a bigger size of dosage for oral case, there is possibility
that
capacity-limited phenomenon would happen. The drug can't be eliminated
proportionally under non-linear case. Therefore, the F may be elevated.
314 Room, 19 Russell Street
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University of Toronto
Toronto, Ontario M5S2S2
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