***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 
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    Input: BACKGROUND We evaluated the effects of cytochrome P450 3A4 ( CYP3A4 ) induction and inhibition on steady-state pharmacokinetics of the components of a novel oral contraceptive ( OC ) containing estradiol valerate ( E₂V ) and dienogest ( DNG ) . STUDY DESIGN CYP3A4 induction was assessed in an open-label , one-arm study . Sixteen healthy postmenopausal women received E₂V 2 mg/DNG 3 mg ( days 1 - 17 ) and concomitant rifampicin ( 600 mg , days 12 - 16 ) . Ratios of the area under the serum concentration-time curve between 0 and 24 h [ AUC(0 - 24 h ) ] and maximum serum concentration ( C(max ) ) of E₂ and DNG on days 17 and 11 ( after and before rifampicin intervention ) are presented . CYP3A4 inhibition was investigated in an open-label , parallel-group study in 24 healthy postmenopausal women receiving E₂V 2 mg/DNG 3 mg ( days 1 - 14 ) and concomitant ketoconazole ( 400 mg , n=12 ) or erythromycin  ( 500 mg three times daily , n=12 ) on days 8 - 14 . Mean ratios of AUC(0 - 24 h ) and C(max ) of E₂ and DNG on days 7 and 14 are presented . RESULTS Concomitant administration of rifampicin  decreased systemic drug exposure and yielded geometric mean ratios for E₂C(max ) and AUC(0 - 24 h ) of 75 % and 56 % , respectively . Corresponding mean ratios for DNG were 48 % and 17 % , respectively  . Ketoconazole coadministration increased systemic drug exposure and yielded ratios of E₂ of 165 % and 157 % , respectively , and ratios of DNG of 194 % and 286 % , respectively . Erythromycin coadministration also result ed in increased mean C(max ) and AUC(0 - 24 h ) of both E₂ and DNG . Geometric mean ratios of C(max ) and AUC(0 - 24 h ) for E₂ were 151 % and 133 % , respectively . Corresponding ratios for DNG were 133 % and 162 % , respectively . CONCLUSIONS Significant drug-drug interactions are apparent when CYP3A4 modulators are coadministered with the components of a novel OC containing E₂V/DNG . Coadministration of CYP3A4 modulators should be avoided where possible , and another type of contraception should be used when coadministration of CYP3A4 inducers like rifampicin is unavoidable The effect of ciprofloxacin , a new broad-spectrum quinolone derivative , on concomitant oral contraceptive steroids has been studied in a double-blind cross-over placebo-controlled r and omized trial . Ten healthy women using long-term oral contraceptive steroids received either ciprofloxacin 500 mg BID or placebo during two consecutive cycles . Therapy was continued for seven days from the first day of contraceptive treatment . FSH , LH and oestradiol blood levels were repeatedly determined to monitor contraceptive steroid efficacy . A seven-day treatment with ciprofloxacin did not affect steroid treatment outcome and appears to be safe in women using this contraceptive method The possibility of escape  ovulation in women using a fluoroquinolone ofloxacin for antibacterial treatment at a dose of 200 mg twice daily for 7 days when taking a combined oral contraceptive ( Microgynon  , 150 μg levonorgestrel and 30 μg ethinyl estradiol ) was studied in 20 women . By using a placebocontrolled , rendomized , cross-over design 6 contraceptive pill cycles were followed . Follicle-stimulating hormone and estradiol concentrations were measured on tablet days 5–8 , 19–21 ; progesterone was assayed on days 19–21 during treatment with ofloxacin or placebo .  Ultrasonographical investigations for measurements of the number and diameter of ovarian follicles were performed on one of days 5–10 , 11–17 , 18–24 , 25–28 . No indications of ovulation during ofloxacin medication were detected . It is concluded that alternative contraceptive pre caution s should not be needed when ofloxacin is prescribed for patients taking oral contraceptives . ResuméOn a étudié la possibilité d'une ovulation fortuite chez une vingtaine de femmes utilisant la fluoroquinoline ofloxacine  pour un traitement antibactérien , selon une dose de 200 mg deux fois par jour pendant 7 jours , en même temps que le contraceptif oral Microgynon ( 150 μg de lévonorgestrel et 30 μg d'éthinyl oestradiol ) . A l'aide d'un contrôle croisé , r and omisé avec placebo , on a suivi 6 cycles pendant lesquels la pilule avait été utilisée . On a mesuré les concentrations de gonadostimuline ( FSH ) et d'oestradiol aux jours 5–8 et 19–21 de la prise des pilules , et on a analysé la progestérone aux jours 19–21 soit durant le traitement à l'ofloxacine soit durant la prise du placebo . Par explorations échographiques , on a mesuré le nombre et le diamètre des follicules ovariens au cours de l'un des jours 5 à 10 , 11 à 17 , 18 à 24 , 25 à 28 . Aucune indication d'ovulation n'a été décelée pendant l'administration de l'ofloxacine . On peut en conclure qu'il ne devrait pas être nécessaire de prendre d'autres pré caution s contraceptives lorsque l'ofloxacine est prescrit à des femmes utilisant les contraceptifs orauxResumenSe estudió en 20 mujeres la posibilidad de ovulación de escape en mujeres a las que se administró una fluoroquinolona , ofloxacin , como tratamiento antibacteriano a una dosis de 200 mg dos veces al día durante 7 días al tomar un anticonceptivo oral combinado , Microgynon ( 150 μg de levonorgestrel y 30 μg de etinilestradiol ) . Utiliz and o un diseño cruzado , aleatorizado y controlado por placebo , se examinaron 6 ciclos con píldora anticonceptiva . Se midieron las concentraciones de folicoestimulina y estradiol en los días de píldora 5–8 , 19–21 ; la progesterona se examinó en los días 19–21 durante et tratamiento con ofloxacin o placebo . Se realizaron investigaciones ecográficas para medir el número y tamaño de los folículos ováricos en uno de los días 5–10 , 11–17 , 18–24 , 25–28 . No se detectó ninguna indicación de ovulación durante la medicación con ofloxacin . Se llegó a la conclusión de que no se necesitan precauciones anticonceptivas adicionales cu and o a las pacientes que toman anticonceptivos orales se les prescribe ofloxacin In view of the considerable debate concerning the possible failure of contraception in women taking broad spectrum antibiotics  , we have examined a group of 12 women aged 22 - 32 in a controlled study . Each woman had been on long-term therapy with oral contraceptive steroids ( OCS ) containing ethynylestradiol ( EE2 ) and levonorgestrel ( Ng ) for at least 6 months and all were in good general health . Blood sample s were taken about 11.0 hours after dosing with their OCS on days 5 , 6 , 7 and 8 of their contraceptive cycle , for measurement of EE2 , Ng , FSH and LH by radioimmunoassay . In addition blood sample s were taken on days 19 , 20 and 21 of the contraceptive cycle for assay of progesterone concentrations in plasma . The study was repeated in the next cycle of use of their OCS during which they took temafloxacin , a broad spectrum quinolone antibiotic in a dose of 600 mg twice daily for 7 days starting on day 1 of the cycle . All women completed the study satisfactorily as judged by diary cards , tablet counts and plasma temafloxacin concentrations . In the early part of the study some nausea and headaches were seen due to taking temafloxacin on an empty stomach but these effects were not seen when the antibiotic was later given with food . There was no evidence of any interaction between temafloxacin and the OCS . The plasma concentration of EE2 was 61.4 + /- 21.1 pg/ml in the control cycle and 68.5 + /- 26.6 pg/ml in the temafloxacin cycle . ( ABSTRACT TRUNCATED AT 250 WORDS Objective To use a novel , sensitive study design to detect a potential oral contraceptive ( OC ) and dirithromycin drug interaction by assessing the pharmacokinetics of the ethinyl estradiol ( E2 ) component of a common OC and the potential failure of OC effectiveness . Methods In this nonblinded study , 20 healthy women using Ortho Novum 7/7/7 - 28 were selected for a three-OC-cycle study . Baseline measures included E2 and progesterone serum levels on days 21 , 23 , 25 , and 27 of cycle one and days 1 , 3 , 5 , and 7 of cycle two . During cycle two , 24-hour blood sampling and radioimmunoassay analysis for ethinyl E2 pharmacokinetics were performed on day 8 and pelvic ultrasound on day 13 . Oral dirithromycin 500 mg/day for 14 days began on day 21 of cycle 2 . After starting dirithromycin , cycle two and three serum E2 , progesterone , and serial ethinyl E2 levels and pelvic ultrasound replicated the baseline schedule . Ovulation was assumed if E2 concentration was greater than 50 pg/mL , progesterone concentration was greater than 3 ng/mL , or if an ovarian cyst greater than 10 mm was present on ultrasound . Results Pharmacokinetic analysis demonstrated a small ( 7.6 % ) but statistically significant decrease ( P = .03 ) in the mean ethinyl E2 24-hour area under the curve and an increase in apparent oral clearance . No woman ovulated , based on E2 levels and progesterone concentrations or ultra sound . Conclusion Dirithromycin increased the apparent oral clearance of ethinyl E2 . The clinical importance of the interaction may be negligible because no woman ovulated or had compromised OC effectiveness in this small series WHAT IS KNOWN AND OBJECTIVE Ulipristal acetate ( UPA ) is a novel selective progesterone receptor modulator for the treatment of benign gynaecological conditions such as uterine myoma . In vitro , it is mainly metabolized by the cytochrome P450 isoenzyme CYP3A4 and to a small extent by CYP1A2 and CYP2D6 . Erythromycin , a macrolide antibiotic , has been shown to be a moderate CYP3A4 inhibitor . Thus , the aim of this study was to determine the effects of erythromycin at steady-state concentrations on the pharmacokinetics of UPA . Effects on the pharmacokinetics of the mono-demethylated metabolite of UPA ( PGL4002 ) were also evaluated . METHODS This was a non-r and omized , single-sequence , two-period , open , single-dose study in 18 healthy female subjects . Subjects received oral UPA ( 20 mg ) once daily on days 1 and 13 and twice-daily erythromycin propionate administrations ( 500 mg ) from days 9 through 17 . RESULTS Geometric mean Cmax and AUCs of UPA were increased by 24 % [ geometric mean ratio point estimate ( 90 % CI ) : 1·24 ( 1·01 - 1·52 ) ] and + 224 % and + 227 % [ geometric mean ratio point estimates ( 90 % CI ) : AUC0-t 3·24 ( 2·75 - 3·83 ) and AUC0-∞ ( 3·27 ( 2·79 - 3·83 ) ] , respectively , with no effect on median tmax or t1/2 . Geometric mean Cmax of PGL4002 was decreased by 47 % [ geometric mean ratio point estimate ( 90 % CI ) : 0·523 ( 0·44 - 0·62 ) ] , but AUCs were increased by + 62 % and + 66 % [ geometric mean ratio point estimates ( 90 % CI ) : AUC0-t 1·62 ( 1·43 - 1·85 ) and AUC0-∞ by 1·66 ( 1·47 - 1·88 ) ] , respectively , with no effect on median tmax . However , geometric mean t1/2.doubled from 24 h to 48 h. No subject was discontinued from the 
    Output:
    
RESULTS : Study quality ranged from good to poor and addressed only oral contraceptive pills , emergency contraception pills , and the combined vaginal ring .
No differences in ovulation suppression or breakthrough bleeding were observed in any study that combined hormonal contraceptives with any antibiotic .
No significant decreases in any progestin pharmacokinetic parameter occurred during co‐administration with any antibiotic .
: Evidence from clinical and pharmacokinetic outcomes studies does not support the existence of drug interactions between hormonal contraception and non‐rifamycin antibiotics .
Most women can expect no reduction in hormonal contraceptive effect with the concurrent use of non‐rifamycin antibiotics