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The following message was posted to: PharmPK
Does anyone out there in PharmPK land have any knowledge of studies
looking at sex (gender) related differences in enzyme inhibition or
induction? I'm interested in CYP3A4, but any info on the subject in
general is welcome. A pubmed search was of no help.
William R. Wolowich, Pharm.D.
College of Pharmacy
Nova Southeastern University
Ft.Lauderdale, FL.
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The following message was posted to: PharmPK
William,
I found these in my files and PubMed.
Some cyp3A4 info included.
Cheers
BC
_
1: Drugs. 1995 Aug;50(2):222-39. Related Articles, Links
Gender effects in pharmacokinetics and pharmacodynamics.
Harris RZ, Benet LZ, Schwartz JB.
Department of Pharmacy, University of California, San Francisco, USA.
2: Clin Pharmacokinet. 2002;41(5):329-42. Related Articles, Links
How important are gender differences in pharmacokinetics?
Meibohm B, Beierle I, Derendorf H.
Department of Pharmaceutical Sciences, College of Pharmacy, University
of Tennessee, Memphis, Tennessee 38163, USA. bmeibohm.aaa.utmem.edu
3. Int J Clin Pharmacol Ther. 1999 Nov;37(11):529-47. Related Articles,
Links
Gender differences in pharmacokinetics and pharmacodynamics.
Beierle I, Meibohm B, Derendorf H.
Department of Clinical Pharmacy, College of Pharmacy, University of
Tennessee, Memphis, USA.
_
Bruce CHARLES, PhD
Reader
School of Pharmacy
The University of Queensland, 4072 Australia
[University Provider Number: 00025B]
TEL: +61 7 336 53194
FAX: +61 7 336 51688
B.Charles.-a-.pharmacy.uq.edu.au
http://www.uq.edu.au/pharmacy/brucecharles/charles.html
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The following message was posted to: PharmPK
William:
Dr Huang at the FDA has published recently on a related issue:
Drug Metab Dispos. 2005 Mar;33(3):426-33. Epub 2004 Dec 17.
Do men and women differ in proximal small intestinal CYP3A or P-
glycoprotein expression?
Paine MF, Ludington SS, Chen ML, Stewart PW, Huang SM, Watkins PB.
General Clinical Research Center, Room 3005, Bldg. APCF, CB#
7600, UNC Hospitals, Chapel Hill, NC 27599-7600, USA. mpaine.-at-.med.unc.edu
The higher systemic clearance of some CYP3A4 [whether also P-
glycoprotein (P-gp)] drug substrates in women versus men is
attributed in part to a higher hepatic CYP3A4 content in women. This,
combined with the general paucity of reported sex differences in the
apparent oral clearance of CYP3A4 substrates, suggested a sex-
dependent expression of CYP3A4 in the intestine, but in a pattern
opposite to that in the liver. Accordingly, duodenal biopsies
obtained from healthy men (n = 46) and women (n = 45) were analyzed,
by Western blot, for relative CYP3A4, as well as for CYP3A5 and P-gp,
expression levels. Among all subjects, CYP3A4 and P-gp varied 8- and
10-fold, respectively. CYP3A5, which was readily detected in 27% of
these predominantly white individuals, varied 7-fold. For all three
proteins, a sex difference was not detected (p >/= 0.55). The lack of
a difference remained for CYP3A4 and P-gp when the analysis was
restricted to white individuals (n = 74) or to individuals with
undetectable CYP3A5. Comparing the 21 premenopausal women (all were
aged <45 years) with the 43 men aged <45 years, again no sex
differences were detected in CYP3A4 and P-gp. Comparing the pre- with
postmenopausal women, mean CYP3A4 content was 20% lower in the
postmenopausal individuals (p = 0.01). The lack of a sex-dependent
difference in proximal intestinal CYP3A4 could account, in part, for
the lack of reported sex differences in the oral, relative to
systemic, clearance of some CYP3A4 substrates. Ramifications of lower
intestinal CYP3A4 content in post- versus premenopausal women require
further investigation.
PMID: 15608139 [PubMed - indexed for MEDLINE]
Sincerely,
Carol Collins MD
Univerisity of Washington
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The following message was posted to: PharmPK
Dear Dr Wolowich,
you might also have a look at:
Benet LZ, Cummins CL, Wu CY.
Unmasking the dynamic interplay between efflux transporters and
metabolic enzymes.
Int J Pharm. 2004; 277:3-9. Review.
Cummins CL, Wu CY, Benet LZ.
Sex-related differences in the clearance of cytochrome P450 3A4
substrates may be caused by P-glycoprotein.
Clin Pharmacol Ther. 2002; 72:474-89. Review.
Best regards
Juergen
--
Juergen Bulitta, MSc
Pharmacometrician, IBMP - Institute for Biomedical and Pharmaceutical
Research
Paul-Ehrlich-Str. 19, D-90562 Nurnberg-Heroldsberg, Germany
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The following message was posted to: PharmPK
There is another good paper just appeared in British Journal of
Clinical
Pharmacology on gender, food and grapefruit effects on the
pharmacokinetics
of the anti-malarial primaquine. Food and grapefruit increased
bioavailability but gender made no difference.
Andrew Sutton
Ref: Bui Tri Cong et al. 2006. Does gender, food or grapefruit juice
alter
the pharmacokinetics of primaquine in healthy subjects. Br J Clin
Pharmacol
61:6 682-689.
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