Vicente et al76
Randomized single blind controlled trial
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24 healthy non-smoking volunteers (12 women and 12 men), 18-35 years
old
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To determine if quinidine induced prolongation of the time from the peak
to the end of the T-wave is greater in women than men
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Subjects received either 4 mg/kg of quinidine IV or a matching placebo
solution over 20 min with 28 blood samples and simultaneous ECGs
collected after drug/placebo infusion for each subject at predetermined
time points over the following 12 h
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- Quinidine causes QTc prolongation and T-wave morphology changes in
both women and men
- Quinidine-induced maximum QTc (541 ± 40 versus 510 ± 38 ms; p = 0.07)
or maximum Tpeak-Tend (216 ±60 versus
222 ± 37 ms; p = 0.76) was similar for men and women
- There was a trend toward a lower maximum serum quinidine concentration
in women compared to men (2.9 ± 0.7 versus 3.7 ± 1.2 μg/mL; p = 0.07)
- The slope describing serum quinidine concentration versus QTc
prolongation was greater in women than in men (38 ± 10 ms/μg/mL vs. 28 ±
9 ms/μg/mL; p = 0.02)
- Differences between women and men occurred primarily in the first 20
min after quinidine infusion, when serum quinidine concentrations were
higher in men than women
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Study Author & Design |
Study Population |
Study Objective |
Methodology |
Results |
Benton et al74
Randomized
single-blinded controlled trial
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24 healthy non-smoking volunteers (12 women and 12 men), 18-35 years
old
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To determine if women have larger increases in QT interval than men at
equivalent serum concentrations of quinidine after intravenous
administration
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Subjects received either 4 mg/kg of quinidine IV or a matching placebo
solution over 20 min. 28 blood samples and simultaneous ECGs were
collected after drug/placebo infusion for each subject at predetermined
time points over the following 48 h
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- There was a trend to greater weight-adjusted clearance of quinidine in
women than in men (5.2 ± 1.1 versus 4.3 ± 1.6 mL/min/kg)
- There was also a trend to a higher maximal plasma concentration of
quinidine in men than in women (3.67 ± 0.13 versus 2.78 ± 0.87 μg/mL; p
= 0.07)
- There were no sex-related differences in the
ratio of the AUC∞ of 3-hydroxyquinidine to the
AUC∞ of quinidine
- The estimated volume of distribution (Vd) at steady
state was not different between the men and women
- There was no difference in the free fraction of quinidine in serum
between men and women
- The free fraction of 3-hydroxyquinidine was slightly higher in women
than in men (0.53 ± 0.05 μg/mL versus 0.47 ± 0.05 μg/mL; p <
.01)
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Study Author & Design |
Study Population |
Study Objective |
Methodology |
Results |
Winchell et al77
A series of open-label, three-period, randomized,
crossover studies
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1. 24 healthy young subjects (mean age: 25.5 years; range: 19-39 years;
16 males and 8 females
2. 18 healthy subjects (mean age: 28.7 years; range: 22-40 years; 8
males, 10 females)
3. 12 elderly subjects (mean age: 71.3 years; range: 65-79 years; 6
males, 6 females
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To investigate the pharmacokinetics and bioavailability
of cyclobenzaprine, including the effects of sex and age
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1. Bioavailability: Subjects received
5 mg orally or 1.25 mg IV cyclobenzaprine
2. Pharmacokinetics: Subjects received a single oral dose of 2.5, 5, or
10 mg cyclobenzaprine
on Day 1 then every 8 h from Days 8
through 14 with final dose on Day 15
3. Pharmacokinetics in aging: Subjects received 5 mg cyclobenzaprine
orally three times daily for 7 days and a final dose on Day 8
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1. Plasma concentrations increased initially, peaking at 4 h post dose,
and then declined slowly
- Mean plasma clearance was 689 ± 216 mL/min - - Mean oral
bioavailability 5 mg tablet formulations were 0.55 (90% CI[0.51,
0.60])
2. There were no statistically significant differences between males and
females for any of the pharmacokinetic parameters
- AUC(0-8 h) and CMax after the last
dose were marginally significantly different
between sexes
3. The population-by-sex effect was marginally
significant for AUC(0-8 h) (p = 0.056) but not for
CMax
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Study Author & Design |
Study Population |
Study Objective |
Methodology |
Results |
El-Eraky et al75
Open trial
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48 healthy volunteers (27 men, 21 women) aged 18-64 years
|
To determine why women are more susceptible to QT interval prolongation
and
torsade de pointes
after administration
of drugs that delay cardiac repolarization
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All subjects took quinidine sulphate capsules 3 mg/kg
orally then ECGs and blood
samples for quinidine concentrations were taken over
24 h following drug administration
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- There were no significant differences in quinidine concentrations
between men and women or in any of the pharmacokinetic variables
measured
- The QTa, and QTc intervals were larger
in females than in males
- Quinidine did not affect QRS duration in women but reduced QRS
duration in men
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Koren et al101
Single‐centre, single dose
open‐label, reference replicate bioavailability study
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12 healthy males and 12 healthy females, 18-45 years with a body mass
index
between 19-30 kg/m2
|
To determine the effect of sex on the pharmacokinetics of
doxylamine–pyridoxine
10 mg–10 mg delayed‐release tablets
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Participants were given doxylamine–pyridoxine
20 mg–20 mg delayed‐release tablets with 240 mL water on an empty
stomach with blood sampling starting 1 h pre‐dose with samples analyzed
using high performance liquid
chromatography‐ tandem mass spectrometry
|
- Females had significantly larger AUC0-t for doxylamine
compared to males
- A higher CMax for doxylamine was observed in females
compared to males
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Study Author & Design |
Study Population |
Study Objective |
Methodology |
Results |
Malhotra et al97
Two randomized double-blind placebo-controlled trials
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1. 32 healthy males aged 18-45 years
2. 16 young men, 16 older men and 16 older women
|
To examine the effect of age, sex and race on the pharmacokinetics,
pharmaco-dynamics and safety profiles of fesoterodine
|
Subjects received either 8 mg of fesoterodine extended release or
placebo with blood samples drawn over 36 h after drug administration and
saliva samples on cotton wool collected over 24 h after drug
administration
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- No apparent differences in CMax,
AUC0-∞, tmax, or mean residual time
between males and females
- Total plasma clearance was highest in young men and lowest in older
women
- Elderly women experienced a 1 g decrease in salivary volume and
elderly men did not 5 h after dose
- Elderly men experienced the greatest residual urinary volume increase
8 h after dose
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Ebert et al102
Open label crossover study
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7 men and 7 women of mean age 23 years and in good health
|
To identify any pharmacokinetic differences between male and female
volunteers in the metabolism of scopolamine when given with grapefruit
juice
|
Each subject received at random scopolamine 0.5 mg IV, scopolamine 0.5
mg orally, or scopolamine 0.5 mg orally mixed with 150 mL fresh
grapefruit juice and blood sampling occurred over the 24 h following
drug administration
|
- CMax was significantly higher in males than females
(6.61 ng/mL versus 3.93 ng/mL) after IV infusion
- All other parameters were similar
|
Study Author & Design |
Study Population |
Study Objective |
Methodology |
Results |
Macleod et al78
Open label study
|
4 men and 5 women aged 21-30 years, and 5 older men and 5 older women
aged 70-88 years
|
To identify age and gender differences in diazepam
pharmacokinetics
|
10 mL blood samples were taken over 1 week after receiving 0.125 mg/kg
diazepam IV over 10 minutes
|
- There was a significant difference in plasma clearance between men and
women (male: 33.2 mL/min and women: 18.1 mL/min)
- The half-life in men (32 h) was significantly shorter than in women
(46.2 h)
- Vd was not significantly different between sexes
|
Bigos et al79
Naturalized prospective study
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332 men and 191 women who were using olanzapine for AD or
schizophrenia
|
To evaluate population pharmacokinetics of olanzapine and factors that
contribute to variability in exposure including sex, race and smoking
status
|
Plasma levels of olanzapine were determined and then used to calculate
non-linear mixed effects modelling for pharmacokinetic analysis
|
- Men cleared olanzapine 38% faster than women (p <0.0001,
unpaired t test)
|
Hartter et al84
Prospective study
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15 male and female participants with major depression
|
To assess sex differences in fluvoxamine serum concentration at two
different fixed dosing regimens (50 twice daily and 100 mg twice
daily)
|
Drug monitoring after 14 days of either treatment
|
- There was a significantly greater increase in fluvoxamine serum
concentration in men than in women when the dose doubled (4.6-fold
versus 2.4-fold increase)
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