Extremely long-range, high-temperature Josephson coupling across a half-metallic ferromagnet.

The Josephson effect results from the coupling of two superconductors across a spacer such as an insulator, a normal metal or a ferromagnet to yield a phase coherent quantum state. However, in junctions with ferromagnetic spacers, very long-range Josephson effects have remained elusive. Here we demonstrate extremely long-range (micrometric) high-temperature (tens of kelvins) Josephson coupling across the half-metallic manganite La0.7Sr0.3MnO3 combined with the superconducting cuprate YBa2Cu3O7. These planar junctions, in addition to large critical currents, display the hallmarks of Josephson physics, such as critical current oscillations driven by magnetic flux quantization and quantum phase locking effects under microwave excitation (Shapiro steps). The latter display an anomalous doubling of the Josephson frequency predicted by several theories. In addition to its fundamental interest, the marriage between high-temperature, dissipationless quantum coherent transport and full spin polarization brings opportunities for the practical realization of superconducting spintronics, and opens new perspectives for quantum computing.

Vectorial Control of the Spin-Orbit Interaction in Suspended InAs Nanowires.

Semiconductor nanowires featuring strong spin-orbit interactions (SOI), represent a promising platform for a broad range of novel technologies, such as spintronic applications or topological quantum computation. However, experimental studies into the nature and the orientation of the SOI vector in these wires remain limited despite being of upmost importance. Typical devices feature the nanowires placed on top of a substrate which modifies the SOI vector and spoils the intrinsic symmetries of the system. In this work, we report experimental results on suspended InAs nanowires, in which the wire symmetries are fully preserved and clearly visible in transport measurements. Using a vectorial magnet, the nontrivial evolution of weak antilocalization (WAL) is tracked through all 3D space, and both the spin-orbit length l SO and coherence length lφ are determined as a function of the magnetic field magnitude and direction. Studying the angular maps of the WAL signal, we demonstrate that the average SOI within the nanowire is isotropic and that our findings are consistent with a semiclassical quasi-1D model of WAL adapted to include the geometrical constraints of the nanostructure. Moreover, by acting on properly designed side gates, we apply an external electric field introducing an additional vectorial Rashba spin-orbit component whose strength can be controlled by external means. These results give important hints on the intrinsic nature of suspended nanowire and can be interesting for the field of spintronics as well as for the manipulation of Majorana bound states in devices based on hybrid semiconductors.

Crystal Phases in Hybrid Metal-Semiconductor Nanowire Devices.

We investigate the metallic phases observed in hybrid metal-GaAs nanowire devices obtained by controlled thermal annealing of Ni/Au electrodes. Devices are fabricated onto a SiN membrane compatible with transmission electron microscopy studies. Energy dispersive X-ray spectroscopy allows us to show that the nanowire body includes two Ni-rich phases that thanks to an innovative use of electron diffraction tomography can be unambiguously identified as Ni3GaAs and Ni5As2 crystals. The mechanisms of Ni incorporation leading to the observed phenomenology are discussed.

Tunable Esaki Effect in Catalyst-Free InAs/GaSb Core-Shell Nanowires.

We demonstrate tunable bistability and a strong negative differential resistance in InAs/GaSb core-shell nanowire devices embedding a radial broken-gap heterojunction. Nanostructures have been grown using a catalyst-free synthesis on a Si substrate. Current-voltage characteristics display a top peak-to-valley ratio of 4.8 at 4.2 K and 2.2 at room temperature. The Esaki effect can be modulated-or even completely quenched-by field effect, by controlling the band bending profile along the azimuthal angle of the radial heterostructure. Hysteretic behavior is also observed in the presence of a suitable resistive load. Our results indicate that high-quality broken-gap devices can be obtained using Au-free growth.

Proximity Driven Commensurate Pinning in YBa2Cu3O7 through All-Oxide Magnetic Nanostructures.

The design of artificial vortex pinning landscapes is a major goal toward large scale applications of cuprate superconductors. Although disordered nanometric inclusions have shown to modify their vortex phase diagram and to produce enhancements of the critical current ( MacManus-Driscoll , J. L. ; Foltyn , S. R. ; Jia , Q. X. ; Wang , H. ; Serquis , A. ; Civale , L. ; Maiorov , B. ; Hawley , M. E. ; Maley , M. P. ; Peterson , D. E. Nat. Mater. 2004 , 3 , 439 - 443 and Yamada , Y. ; Takahashi , K. ; Kobayashi , H. ; Konishi , M. ; Watanabe , T. ; Ibi , A. ; Muroga , T. ; Miyata , S. ; Kato , T. ; Hirayama , T. ; Shiohara , Y. Appl. Phys. Lett. 2005 , 87 , 1 - 3 ), the effect of ordered oxide nanostructures remains essentially unexplored. This is due to the very small nanostructure size imposed by the short coherence length, and to the technological difficulties in the nanofabrication process. Yet, the novel phenomena occurring at oxide interfaces open a wide spectrum of technological opportunities to interplay with the superconductivity in cuprates. Here, we show that the unusual long-range suppression of the superconductivity occurring at the interface between manganites and cuprates affects vortex nucleation and provides a novel vortex pinning mechanism. In particular, we show evidence of commensurate pinning in YBCO films with ordered arrays of LCMO ferromagnetic nanodots. Vortex pinning results from the proximity induced reduction of the condensation energy at the vicinity of the magnetic nanodots, and yields an enhanced friction between the nanodot array and the moving vortex lattice in the liquid phase. This result shows that all-oxide ordered nanostructures constitute a powerful, new route for the artificial manipulation of vortex matter in cuprates.

[Protection of working woman's health]. / Tutela della salute della donna lavoratrice.

INTRODUCTION: In the past the role of women was mainly that of wife and mother, over the centuries, this role has changed: women assert themselves in every social field and workplace. OBJECTIVES: Analyze the history of women's work, from prehistory to the present day highlighting the evolution of women's role over the centuries. Identify which may be the different occupational stressors, in particular the organizational and psycho-social ones, to which is submitted a working woman. MATERIALS AND METHODS: The authors have analyzed the most relevant data from literature, in particular on the issue of mental health. RESULTS: Provide the main forms of prevention that have to be implemented. DISCUSSION: The main challenge for women today, is to balance work outside the home and housework. This added to job stressors, may interfere with the psychological and physical wellbeing of the worker.

Different performance of platform switching in equicrestal position implant: an histological study.

OBJECTIVE: In this study we tested two different type of implant systems that were selected on the basis of differences in macrogeometry of platform switching in order to evaluate the behavior in term of BIC on the platform. MATERIAL AND METHOD: The patients were divided in two groups (Group I and II); group I was composed by 4 patients that each received in the posterior areas of mandible one type A implant (3,6 mm in diameter and 6,5 mm in length GTBPlan1Health Amaro (UD) Italy) one type B implant (4 mm in diameter and 8 mm in length OsseoSpeed Astra Tech, Dentsply Molndal, Sweden). Group II was composed by 3 patients that each received in the posterior areas of jawsbone one type A implant [3,6 mm in diameter and 6,5 mm in length GTB- Plan1Health Amaro, (UD), Italy] one type B implant (4 mm in diameter and 8 mm in length OsseoSpeed Astra Tech, Dentsply Molndal, Sweden). All the implants were placed, by the same operator, in equicrestal position using "one stage" technique with a healing abutment at an adequate gingival height. After 12 weeks of healing all the implants of both groups were harvested with the peri-implant bone tissues. BIC upon platform was calculated considering as implant surface the platform length. RESULTS: Our results showed that the mean percentage of BIC value related to platform surface placed in equicrestal position was higher in patients with type A implant than patients receiving type B implant independently from mandibular or maxillary positions. Moreover the mean percentage of BIC related to platform surface was significantly (p<0.05) higher in Group II/A than Group I/A. CONCLUSIONS: Our data highlights that the particular features of the Bioplatform of Type A implant systems guarantee a higher value of BIC even if the implants were placed equicrestally.

Local noise in a diffusive conductor.

The control and measurement of local non-equilibrium configurations is of utmost importance in applications on energy harvesting, thermoelectrics and heat management in nano-electronics. This challenging task can be achieved with the help of various local probes, prominent examples including superconducting or quantum dot based tunnel junctions, classical and quantum resistors, and Raman thermography. Beyond time-averaged properties, valuable information can also be gained from spontaneous fluctuations of current (noise). From these perspective, however, a fundamental constraint is set by current conservation, which makes noise a characteristic of the whole conductor, rather than some part of it. Here we demonstrate how to remove this obstacle and pick up a local noise temperature of a current biased diffusive conductor with the help of a miniature noise probe. This approach is virtually noninvasive for the electronic energy distributions and extends primary local measurements towards strongly non-equilibrium regimes.

Amrinone in the treatment of chronic cardiac failure.

The efficacy and safety of oral amrinone were examined in 17 patients with moderately severe to severe heart failure that was refractory to standard medical therapy and vasodilators. The short-term and 28 week response to open amrinone therapy was assessed first, followed by a placebo-controlled, double-blind withdrawal study of two 13 week stages in nine patients. Rest and exercise ventricular function were determined before and after 32 hours of amrinone; aerobic capacity was serially assessed. After 2 hours, 1.64 mg/kg amrinone produced a 40% (p less than 0.001) increase in cardiac output and a 32% (p less than 0.02) decrease in pulmonary wedge pressure without altering heart rate or blood pressure. The exercise cardiac index-wedge pressure curve obtained 32 hours after the first oral dose was significantly shifted (p less than 0.05) above control values. A sustained improvement in maximal oxygen uptake was noted during long-term open amrinone therapy. Subsequently, seven of the patients randomized to placebo therapy had a significant deterioration of symptoms or exercise tolerance, or both. After 4 weeks of readministration of amrinone, clinical stability was once again established and exercise tolerance was improved by Weeks 8 to 16. Adverse effects of thrombocytopenia (one patient) and hepatic dysfunction (one patient) attributable to amrinone were observed. It is concluded that amrinone is effective in the long-term treatment of chronic cardiac failure.

Trimethoprim inhibition of the renal clearance of procainamide and N-acetylprocainamide.

To test the effect of trimethoprim (an antibiotic commonly administered with sulfamethoxazole) on the disposition of the antiarrhythmic procainamide hydrochloride and its active metabolite N-acetylprocainamide, 10 healthy men received 1 g of procainamide hydrochloride orally on two occasions, coadministered with placebo or trimethoprim (100 mg twice a day for 2 days before and then 200 mg with the procainamide dose). Trimethoprim decreased the mean (+/- SD) renal clearance by 45% after the dose of procainamide was administered (487 +/- 129 vs 267 +/- 123 mL/min) and that of N-acetylprocainamide by 26% (275 +/- 78 vs 192 +/- 82 mL/min) compared with placebo. The mean area under plasma concentration--time curve 0 to 12 hours after dosing increased 39% for procainamide (19.8 +/- 4.8 vs 27.6 +/- 7.2 mg.h/L) and 27% for N-acetylprocainamide (9.1 +/- 2.1 vs 11.4 +/- 2.8 mg.h/L). The corrected QT electrocardiographic interval at 2 hours after the procainamide dose was 0.40 +/- 0.02 second with placebo and 0.43 +/- 0.03 second with trimethoprim. Trimethoprim may increase procainamide and N-acetylprocainamide plasma concentrations, resulting in increased pharmacodynamic response apparently caused by the competition for renal tubular cationic secretion.

The influence of micro and macro-geometry in term of bone-implant interface in two implant systems: an histomorphometrical study.

OBJECTIVE: Many factors could affect the osseous healing of implants such as surface topography of biomaterial, the status of the bone/implant site, implant loading conditions, surgical technique and implant design. The aim of this study was to analyze the BIC of 2 different implants systems characterized by different micro and macrogeometry, that were placed in the posterior maxillary and mandibular jaws of humans, clinically unloaded and retrieved for histomorphometric analyses after 12 weeks. MATERIAL AND METHOD: The patients were divided in two groups (Group I and II); group I was composed by 4 patients that each received in the posterior areas of mandible one type A implant [GTB-Plan1Health Amaro (UD) Italy] one type B implant (OsseoSpeed Astra Tech, Dentsply Molndal, Sweden). Group II was composed by 3 patients that each received in the posterior areas of jawsbone one type A implant [GTB-Plan1Health Amaro (UD) Italy] one type B implant (OsseoSpeed Astra Tech, Dentsply Molndal, Sweden). After 12 weeks of healing all the implants of both groups were harvested with the peri-implant bone tissues. Osseointegration process was evaluated throughout measurements of BIC. RESULTS: No statistical significance differences were found among the mean percentage of BIC of Group I - type A were 66,51% versus 49,96% in Group I - type B, as well as among the mean percentage of BIC of Group II - type A were 43.7% versus 60.02% in Group II - type B. CONCLUSIONS: Our results highlight that the mean percentage of BIC after 12 weeks from the implants placement without functional loading is not influenced by the composition of the implant surface.

Paving the way to nanoionics: atomic origin of barriers for ionic transport through interfaces.

The blocking of ion transport at interfaces strongly limits the performance of electrochemical nanodevices for energy applications. The barrier is believed to arise from space-charge regions generated by mobile ions by analogy to semiconductor junctions. Here we show that something different is at play by studying ion transport in a bicrystal of yttria (9% mol) stabilized zirconia (YSZ), an emblematic oxide ion conductor. Aberration-corrected scanning transmission electron microscopy (STEM) provides structure and composition at atomic resolution, with the sensitivity to directly reveal the oxygen ion profile. We find that Y segregates to the grain boundary at Zr sites, together with a depletion of oxygen that is confined to a small length scale of around 0.5 nm. Contrary to the main thesis of the space-charge model, there exists no evidence of a long-range O vacancy depletion layer. Combining ion transport measurements across a single grain boundary by nanoscale electrochemical strain microscopy (ESM), broadband dielectric spectroscopy measurements, and density functional calculations, we show that grain-boundary-induced electronic states act as acceptors, resulting in a negatively charged core. Besides the possible effect of the modified chemical bonding, this negative charge gives rise to an additional barrier for ion transport at the grain boundary.

Use of midazolam urinary metabolic ratios for cytochrome P450 3A (CYP3A) phenotyping.

Midazolam (MDZ) total clearance (ClT) is widely used for cytochrome P450 3A (CYP3A) phenotyping, but requires up to eight blood samples. This study was conducted to compare the use of midazolam ClT to use of a midazolam urinary metabolic ratio for CYP3A phenotyping. Ten male and 10 female subjects received i.v. midazolam 0.025 mg/kg eight times over a 4-month period at approximately 2-week intervals. The first six phenotyping measures were used to estimate baseline CYP3A activity, then subjects received the moderate CYP3A inhibitor fluvoxamine 150 mg/day for the last 4 weeks (two phenotyping visits) of the study. Serial blood samples were obtained for calculation of ClT. Urine was collected for 6 h following each midazolam dose. Midazolam, 1'-hydroxymidazolam (1-OHMDZ), and 4-hydroxymidazolam were measured in plasma and urine by liquid chromatography with tandem mass spectrometry (LC/MS/MS). Analysis of 148 samples from 20 subjects revealed a weak overall correlation between the urinary ratio of 1-OHMDZ/MDZ to midazolam ClT of r(s) = 0.372 (P = 0.0001). There was no correlation when examining either baseline samples or fluvoxamine-inhibited samples alone (r(s) = 0.101, P = 0.289 and r(s) = 0.266, P = 0.123, respectively). The median (range) urinary ratio decreased significantly with fluvoxamine [219 (141-409) versus 127 (50-464); P = 0.005] and to a similar extent to the midazolam ClT (-33.6% versus -42.4%, respectively; P > 0.05). Median urinary recovery of the i.v. midazolam dose varied between 1.4% and 53% and was significantly lower in samples collected while patients were receiving fluvoxamine (34.3% versus 23.1%; P= 0.0004). Based on these results, although this midazolam urinary ratio was not very reflective of baseline CYP3A activity, it may be a useful indicator of CYP3A inhibition.

Trimethoprim alters the disposition of procainamide and N-acetylprocainamide.

The steady-state pharmacokinetics and pharmacodynamics of procainamide and its active N-acetyl metabolite (NAPA) were assessed alone and in combination with trimethoprim. Eight healthy men received oral sustained-release procainamide, 500 mg every 6 hours for 3 days, alone and with oral trimethoprim, 200 mg daily for 4 days. Concomitant trimethoprim significantly increased the plasma AUC(0-12) of both procainamide and NAPA (63% and 52%, respectively), with concurrent decreases in their renal clearances (47% and 13%, respectively) and a 39% increase in the mean urinary recovery of NAPA (as percentage of procainamide and NAPA recovery). After trimethoprim coadministration, there was also a trend toward a decrease in the apparent acetylation clearance of procainamide (19%, p = 0.057). The change in procainamide and NAPA renal clearances after trimethoprim coadministration strongly correlated with their baseline renal clearances (r = 0.84 and r = 0.74, respectively, p less than 0.0001). There was small but significant increase in the corrected QT interval with procainamide administration, which increased further with trimethoprim coadministration. We conclude that trimethoprim increases the plasma concentrations of procainamide and NAPA by decreasing their renal clearances and allowing more conversion of procainamide to NAPA.

Effect of food on the absorption of enteric-coated aspirin: correlation with gastric residence time.

The Heidelberg capsule is an indigestible indicator of gastrointestinal pH, which was used to evaluate the relationship between gastric residence time (GRT) and variability in aspirin absorption from enteric-coated tablets. In a crossover study, eight healthy subjects (four men and four women) received an enteric-coated aspirin (648 mg) together with a Heidelberg capsule while fasting or with food (breakfast, followed 4 hours later by lunch). Salicylic acid and salicyluric acid concentrations in plasma and urine were measured by HPLC. The mean (+/- SD) GRT was significantly delayed by food (0.8 +/- 0.5 vs. 5.9 +/- 3.3 hours; P less than 0.005). The mean (+/- SD) lag time (TL) and time to peak concentration (expressed as salicylic acid equivalents) were markedly prolonged after the fed regimen (2.7 +/- 0.8 vs. 8.9 +/- 3.7 hours [P less than 0.005] and 8.3 +/- 2.9 vs. 13.8 +/- 4.5 hours [P less than 0.025]). For the combined data from the fasting and fed evaluations, an excellent correlation existed between TL and GRT of the capsule (TL = 1.0 GRT + 1.95; n = 16; r = 0.94; P less than 0.0001). Women demonstrated greater delays in GRT and TL than did men. The delay in aspirin absorption from an enteric-coated tablet is directly related to its GRT, which is gender related and greatly affected by food.

Food-induced gastric retention and absorption of sustained-release procainamide.

The relationship between variations in the gastric residence time and the absorption of procainamide from a waxed matrix, sustained-release tablet was evaluated in a repeated-measures study conducted in eight healthy men. Subjects received sustained-release procainamide together with a Heidelberg capsule, alone and with food. Blood and urine samples were collected for up to 24 hours before and after gastric emptying of the Heidelberg capsule for procainamide and N-acetylprocainamide concentration determinations. The gastric residence time of the Heidelberg capsule was prolonged by food (median 3.5 [range 1.5 to 10.0] vs. 1.0 [range 0.5 to 2.5] hours; P less than 0.02). No significant differences (median [range]; fasting vs. fed) in procainamide lag time (0.5 [0.5 to 1.0] vs. 0.5 [0.5 to 1.5] hours) or time at which peak procainamide plasma concentrations occurred (2.9 [1.0 to 4.3] vs. 2.8 [2.0 to 6.0] hours) were evident with feeding. Slight increases in procainamide AUC and peak concentrations occurred with feeding. No alteration in the extent of urinary excretion of procainamide or N-acetylprocainamide occurred with feeding. Thus food did not influence the absorption of sustained-release procainamide despite apparent prolonged gastric retention.

Comparative evaluation of the effects of isradipine and diltiazem on antipyrine and indocyanine green clearances in elderly volunteers.

Calcium antagonists have been shown to depress hepatic enzymes and accelerate hepatic blood flow. This study was designed to compare the effects of two calcium antagonists, isradipine and diltiazem, on antipyrine and indocyanine green (ICG) clearances in the elderly. Eighteen elderly subjects (aged 65 to 80 years) received either isradipine (5 mg every 12 hours), diltiazem (90 mg every 8 hours), or placebo (every 12 hours) for 4 days. On the third day after the study treatment, a 0.5 mg/kg dose of ICG was administered. Blood samples were obtained over 20 minutes for HPLC determination of ICG plasma concentrations. Ten minutes later, subjects ingested 1.2 gm antipyrine. Blood samples were obtained over 48 hours for HPLC determination of antipyrine plasma concentrations. Mean +/- SD antipyrine clearance after diltiazem (0.0258 +/- 0.0065 L/hr/kg) was significantly lower than that observed after isradipine (0.0334 +/- 0.0098 L/hr/kg) or placebo (0.0329 +/- 0.0082 L/hr/kg). Antipyrine clearance after isradipine was not significantly different from that after placebo. Mean +/- SD ICG clearances after diltiazem (9.17 +/- 1.35 ml/min/kg) or isradipine (9.57 +/- 1.82 ml/min/kg) were significantly higher than that observed after placebo (8.06 +/- 1.45 ml/min/kg). These findings suggest that diltiazem, but not isradipine, affects hepatic enzyme activity in the elderly. Both agents accelerate ICG clearance, a marker of hepatic blood flow.

Effects of cimetidine and ranitidine on the conversion of prednisone to prednisolone.

Prednisone is a glucocorticoid that must be converted in vivo to prednisolone for pharmacologic activity. We examined the effects of the H2-receptor antagonists cimetidine and ranitidine on the time course of plasma prednisolone concentrations after an oral dose of prednisone. Nine healthy men received each of three oral treatments in a double-blind, balanced, crossover manner: cimetidine (300 mg every 6 hours), ranitidine (150 mg twice a day), or placebo for 4 days, with prednisone (40 mg) taken also on day 4. Serial blood and urine samples were collected for 30 hours after prednisone dosing. Prednisone and prednisolone plasma and urine concentrations were analyzed by HPLC. No differences were found between treatments in the maximum prednisolone plasma concentration, t1/2, apparent volume of distribution, and AUC. Cimetidine reduced the mean (+/- SD) ratio of prednisone dose to the plasma prednisolone AUC (16.6 +/- 2.9 L/hr) below that ratio after ranitidine (19.2 +/- 4.2 L/hr) and placebo (19.3 +/- 2.8 L/hr), and resulted in the lowest fractional excretion of prednisolone in the urine (5.2% +/- 2.2%, 9.8% +/- 4.5%, and 12.4% +/- 4.9%, respectively). The minor alterations in prednisolone kinetics during concomitant cimetidine dosing are not likely to induce clinically significant alterations in steroid effect.

Clinical evaluation of a benzofuroquinolizine alpha 2-adrenoceptor antagonist.

The pharmacodynamics of MK-912, a benzofuroquinolizine alpha-adrenoceptor antagonist, were evaluated in healthy male volunteers. Eight subjects were treated with single oral doses of 0.1, 1.0, and 2.0 mg MK-912 and with a placebo in a four-period, double-blind, balanced, crossover study. Hemodynamic effects were observed with the 2.0 mg dose of MK-912 (peak increase from baseline in systolic and diastolic blood pressure +/- SEM, 14.8/9.2 +/- 2.9/2.1 mm Hg; peak increase in heart rate, 6.3 +/- 2.1 beats/min; p less than 0.05 versus placebo). Plasma concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG, a catecholamine metabolite) were increased 29% +/- 7% and 40% +/- 10% above baseline 2 hours after administration of 1.0 and 2.0 mg MK-912, respectively (p less than 0.01 compared with placebo). A modest dose-dependent reduction (5% to 10%) in fasting plasma glucose concentration was observed 1/2 to 1 hour after administration of 1.0 and 2.0 mg MK-912 (p less than 0.05 compared with placebo), without significant change in plasma insulin values. MK-912 was well tolerated, although it did have a mild anxiogenic effect. MK-912 is a potent, orally active agent with a pharmacologic profile consistent with alpha 2-adrenoceptor antagonism.

Quantification of 3-month intraindividual variability and the influence of sex and menstrual cycle phase on CYP3A activity as measured by phenotyping with intravenous midazolam.

OBJECTIVE: Intraindividual variability and the effects of sex and menstrual cycle phase on CYP3A activity were evaluated by phenotyping with use of midazolam as the probe drug. METHODS: Midazolam (0.025 mg/kg) was administered intravenously to 10 white male volunteers every 14 days for 3 months and to 10 white premenopausal female volunteers during the midfollicular and midluteal phases of the menstrual cycle for 3 complete cycles. Serum was collected for a 6-hour period, and enzyme activity was represented by midazolam plasma clearance. RESULTS: No difference in clearance was observed during the menstrual cycle phases. Mean +/- SD midazolam clearance was 0.00816 +/- 0.00252 L/min/kg during the midfollicular phase and 0.00818 +/- 0.00224 during the midluteal phase (P = .96). When the menstrual cycle phases were combined, mean midazolam clearance in women was 0.00817 +/- 0.00235 L/min/kg. Mean male midazolam clearance was 0.00766 +/ 0.00167 L/min/kg. There was no difference in midazolam clearance between men and women (P = .68). Coefficients of variation (CV%) for the 6 phenotyping visits were calculated and the median midazolam clearance CV% (25th to 75th percentile) was 9.75% (8.40% to 11.5%). CONCLUSIONS: Because no significant differences in midazolam clearance were noted between menstrual cycle phases or between sexes, pharmacokinetic and clinical investigations of CYP3A activity in adults may not require stratification on the basis of menstrual cycle phase or sex.