***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Adverse effects of drugs are poorly reported in the literature . The aim of this study was to examine the frequency of the adverse events of antiepileptic drugs ( AEDs ) , in particular carbamazepine ( CBZ ) and oxcarbazepine ( OXC ) in patients with neuralgiform pain using the psychometrically tested Liverpool Adverse Events Profile ( AEP ) and provide clinicians with guidance as to when to change management . Methods The study was conducted as a clinical prospect i ve observational exploratory survey of 161 patients with idiopathic trigeminal neuralgia and its variants of whom 79 were on montherapy who attended a specialist clinic in a London teaching hospital over a period of 2 years . At each consultation they completed the AEP question naire which provides scores of 19–76 with toxic levels being considered as scores > 45 . Results The most common significant side effects were : tiredness 31.3 % , sleepiness 18.2 % , memory problems 22.7 % , disturbed sleep 14.1 % , difficulty concentrating and unsteadiness 11.6 % . Females reported significantly more side effects than males . Potential toxic dose for females is approximately 1200 mg of OXC and 800 mg of CBZ and 1800 mg of OXC and 1200 mg of CBZ for males . Conclusions CBZ and OXC are associated with cognitive impairment . Pharmacokinetic and pharmacodynamic differences are likely to be the reason for gender differences in reporting side effects . Potentially , females need to be prescribed lower dosages in view of their tendency to reach toxic levels at lower dosages . Side effects associated with AED could be a major reason for changing drugs or to consider a referral for surgical management The impact of gender , use of oral contraceptive steroids ( OCS )  , coffee consumption and of smoking on the metabolism of sparteine , caffeine , and paracetamol was studied in 194 r and omly selected subjects ( 98 male and 95 female ) . Thirty-eight of the male volunteers were cigarette smokers , 40 of the female subjects were smokers and /or users of OCS .  The metabolic ratio of sparteine oxidation ( MRs ) showed a trimodal distribution . 7.7 % of the subjects had a MRs > 20 and thus were poor metabolizers ( PMs ) . Within the extensive metabolizer ( EM ) subjects , a distinct subgroup accounting for 11 % was observed with 20 > MRs > 1.2 . Six of the 15 phenotypical PMs were heterozygous EMs by genotyping . This indicates the existence of one or several CYP2D6 mutations which can not be identified by the currently employed genotyping methods . In each subgroup , i.e. smokers/OCS and non-smokers/non-OCS , the cumulative frequency distribution of the heterozygous ( wt/B ) phenotype caused a shift to higher MRs compared with the wild-type homozygotes ( wt/wt ) . Thus , for the in vivo activity of CYP2D6 , genetic determinants prevail over environmental factors . Smoking , use of oral contraceptive steroids , caffeine consumption , or gender had no influence on sparteine metabolism . The distribution of the paracetamol glucuronide/paracetamol metabolic ratio appeared to be unimodal although skewed . Glucuronidation capacity was clearly affected by gender , OCS use and smoking . It was higher in male than in female subjects . Male smokers had the highest , and female non-smokers/non-OCS users the lowest metabolic ratio . CYP1A2 activity , as determined by a caffeine metabolic ratio ( ( AFMU + 1X + 1U)/1 , 7U ) , was multimodally distributed and was clearly increased in smokers . It was significantly correlated to paracetamol glucoronidation in male heavy smokers ( r=0.85 ) , suggesting an element of co-regulation of CYP1A2 and of paracetamol conjugating UDP-glucuronosyltransferase isozymes , including UGTI.6 BACKGROUND Amiodarone use was associated with an increased need for pacemaker insertion in a retrospective study of patients with atrial fibrillation ( AF ) and prior myocardial infa rct ion . The aims of this study were to determine prospect ively whether amiodarone increases the need for pacemakers in a general population of patients with AF and whether this effect is modified by sex . METHODS The study included 1005 patients with new-onset AF who were enrolled in the Fibrillation Registry Assessing Costs , Therapies , Adverse events , and Lifestyle ( FRACTAL ) .  Multivariable Cox regression models , including time-dependent covariates accounting for medication exposure , were used to evaluate the risk of pacemaker insertion associated with amiodarone use . RESULTS Amiodarone use was associated with an increased risk of pacemaker insertion ( hazard ratio [ HR ] , 2.01 ; 95 % confidence interval [ CI ] , 1.08 - 3.76 ) after adjustment for age , sex , atrial flutter , coronary artery disease , heart failure , and hypertension . The effect of amiodarone use was modified by sex , with a significant risk in women but not in men ( HR , 4.69 ; 95 % CI , 1.99 - 11.05 vs HR , 1.05 ; 95 % CI , 0.42 - 2.58 [ P = .02 ] ) . This interaction remained significant after adjustment for weight , body mass index , weight-adjusted amiodarone dose , and use of other antiarrhythmic or rate control drugs . CONCLUSION The risk of bradyarrhythmia requiring pacemaker insertion associated with amiodarone use for AF is significantly greater in women than in men , independent of weight or body mass index Purpose Data from two clinical studies ( hyperCholesterolaemia in cHildren and Adolescents taking Rosuvastatin OpeN label [ CHARON ; NCT01078675 ] and Study 4522IL/0086 ) were used to describe rosuvastatin pharmacokinetics in patients with heterozygous familial hypercholesterolemia aged ≥6 to < 18 years . Methods Rosuvastatin concentration – time data were analyzed via non-linear mixed-effects modeling ( NONMEM ) , with clearance ( CL/F ) as the pre-defined key pharmacokinetic parameter of interest . In addition , descriptive comparisons between pediatric patients and adults ( healthy and dyslipidemic ) were performed . The data set included 214 pediatric patients , with 2,029 rosuvastatin concentrations . Results A linear two-compartment model with first-order absorption and elimination processes adequately described the combined data set . Weight and gender were significant covariates for CL/F , with moderate between-patient variability remaining ( coefficient of variation ( CV ) 40 % ): CL/F in female children was approximately 30 % lower than in male children , and there was a twofold mean difference in CL/F across the observed weight range . Age was not a significant covariate after accounting for weight and gender differences . However , weight and gender only reduced between-patient variability from 45 ( without covariates ) to 40 % and are considered unlikely to be clinical ly relevant . Conclusions Rosuvastatin pharmacokinetics appeared generally predictable with respect to dose , and time ( study duration ) and the exposure ( dose-normalized area under the plasma concentration – time curve at steady state ( AUCss ) ) in children and adolescents appeared to be similar or lower than adult patients with dyslipidemia PURPOSE Encenicline ( EVP-6124 ) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in Alzheimer 's disease and schizophrenia . We report on 2 single-dose studies to assess the relative bioavailability , pharmacokinetic profile , tolerability , and cognitive effects of encenicline in healthy volunteers . METHODS A single ascending-dose study assessed the safety , tolerability , pharmacokinetic , and pharmacodynamic profiles of encenicline in healthy male volunteers . Subjects received a single 1- , 3.5- , 7- , 20- , 60- , or 180-mg oral solution dose of encenicline or placebo . A second single-dose , r and omized , open-label , 3-period , crossover study in healthy male and female subjects compared the relative bioavailability of a 1-mg oral capsule versus a 1-mg oral solution dose of encenicline and evaluated the effects of food and sex on encenicline pharmacokinetic profile . FINDINGS In the first study ,  encenicline was well tolerated and dose-proportional increases in C(max ) ( mean range 0.59 - 100 ng/mL ) and AUC0-∞ ( mean range 45.6 - 8890 ng·h/mL ) were observed over a 1- to 180-mg dose range . Procognitive effects on the Digit Symbol Substitution Test were maximal at the 20-mg dose . In the second study , encenicline 1-mg oral capsules and oral solution were bioequivalent and there was no observed food effect on encenicline pharmacokinetic profile with the 90 % confidence intervals of the treatment ratios for both comparisons ( ie , capsule to solution and fed to fasted ) for Cmax and AUC being within 80 % to 125 % . A 30 % to 40 % higher encenicline  exposure in female subjects than respective values in male subjects was consistent with a 33 % higher weight of the male subjects . No clinical ly relevant safety profile or tolerability effects of encenicline  were observed . IMPLICATION S Encenicline was well tolerated at single doses up to 180 mg , and doses as low as 1 mg had dose- and time-dependent pharmacodynamic effects on the central nervous system . Oral capsule and solution were bioequivalent and were not affected by food . Although a sex effect on pharmacokinetic profile was observed , it was attributable to weight differences . Clinical Trial Registration at EudraCT : 2006 - 005623 - 42 and EudracT : 2008 - 000029 - 20 STUDY OBJECTIVES To compare the steady-state pharmacokinetics and safety of saquinavir soft-gelatin capsules ( SGC ) plus low-dose ritonavir administered once/day in antiretroviral-naive adult patients infected with the human immunodeficiency virus type 1 ( HIV-1 ) and to evaluate any sex-related differences . DESIGN Single-center , open-label , pharmacokinetic study . SETTING University-affiliated outpatient HIV clinic . PATIENTS Six men and seven women with HIV-1 . INTERVENTION Each patient received saquinavir SGC 1600 mg and ritonavir 100 mg for a 14-day course of therapy . Nine serial blood sample s during 24 hours were collected on day 14 of therapy MEASUREMENTS AND MAIN RESULTS Plasma saquinavir and ritonavir concentrations were measured by high-performance liquid chromatography . St and ard noncompartmental methods were used to calculate the pharmacokinetic parameters . The unpaired Student t test was used for the statistical comparison of pharmacokinetic parameters between male and female patients . Once-daily saquinavir SGC plus ritonavir was generally well tolerated . Pharmacokinetic data from five men and five women were evaluable . The median saquinavir area under the concentration-time curve from 0 - 24 hours ( AUC0 - 24 ) in the female patients ( 82,300 ng x hr/ml ) was significantly ( p=0.036 ) higher than that in the male patients ( 47,400 ng x hr/ml ) . This relationship remained significant for weight-adjusted saquinavir AUC0 - 24 values . Ritonavir 's apparent oral clearance in the women was significantly ( p=0.023 ) lower than that in the men . CONCLUSION Significantly higher plasma concentrations of saquinavir  were achieved in female compared with male HIV-infected patients receiving once-daily saquinavir SGC 1600 mg plus ritonavir 100 mg STUDY OBJECTIVE To examine the comparative pharmacokinetics of long-term methylprednisolone therapy in black and white renal transplant recipients . DESIGN Comprehensive pharmacokinetic evaluations of patients who participated in our glucocorticoid-monitoring program . SETTING University-based renal transplantation clinic . PATIENTS Six white renal transplant recipients with stable renal function , sex- and ( approximate ) age-matched with six preselected black patients . INTERVENTIONS The daily oral methylprednisolone dose for each patient was administered intravenously , and serial plasma sample s were obtained over 24 hours . MEASUREMENTS AND MAIN RESULTS Methylprednisolone was analyzed by high-performance liquid chromatography . The drug 's pharmacokinetics in black and white patients , respectively , were as follows : mean clearance 234 + /- 124 and 472 + /- 180 ml/hr/kg ( p < 0.05 ) ; volume of distribution 0.3 - 2.0 and 0.8 - 2.0 L/kg ; and elimination 
    Output:
    
We observed that female generally has a lower the gastric emptying time , gastric PH , lean body mass , and higher plasma volume , BMI , body fat , as well as reduce hepatic clearance , difference in activity of Cytochrome P450 enzyme , and metabolize drugs at different rate compared with male .
However , these differences can lead to adverse effects in female especially for the pregnant , post-menopausal , and elderly women .
Conclusion This systematic review provides an evidence for the effectiveness of dosage difference to ensure safety and efficient treatment .