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Browsing by Author "Hogg, Graham"
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Item Forced expiratory flows and diffusion capacity in infants born from mothers with pre‐eclampsia(Wiley, 2022) Ren, Clement L.; Slaven, James E.; Haas, David M.; Haneline, Laura S.; Tiller, Christina; Hogg, Graham; Bjerregaard, Jeffrey; Tepper, Robert S.; Biostatistics, School of Public HealthRationale: Animal models suggest pre-eclampsia (Pre-E) affects alveolar development, but data from humans are lacking. Objective: Assess the impact of Pre-E on airway function, diffusion capacity, and respiratory morbidity in preterm and term infants born from mothers with Pre-E. Methods: Infants born from mothers with and without Pre-E were recruited for this study; term and preterm infants were included in both cohorts. Respiratory morbidity in the first 12 months of life was assessed through monthly phone surveys. Raised volume rapid thoracoabdominal compression and measurement of diffusion capacity of the lung to carbon monoxide (DLCO) were performed at 6 months corrected age. Measurements and main results: There were 146 infants in the Pre-E cohort and 143 in the control cohort. The Pre-E cohort was further divided into nonsevere (N = 41) and severe (N = 105) groups. There was no significant difference in DLCO and DLCO/alveolar volume among the three groups. Forced vital capacity was similar among the three groups, but the nonsevere Pre-E group had significantly higher forced expiratory flows than the other two groups. After adjusting for multiple covariates including prematurity, the severe Pre-E group had a lower risk for wheezing in the first year of life compared to the other two groups. Conclusions: Pre-E is not associated with reduced DLCO, lower forced expiratory flows, or increased wheezing in the first year of life. These results differ from animal models and highlight the complex relationships between Pre-E and lung function and respiratory morbidity in human infants.Item Pharmacokinetics of vaginal versus buccal misoprostol for labor induction at term(Wiley, 2022) Vorontsova, Yana; Haas, David M.; Flannery, Kathleen; Masters, Andrea R.; Silva, Larissa L.; Pierson, Rebecca C.; Yeley, Brittany; Hogg, Graham; Guise, David; Heathman, Michael; Quinney, Sara K.; Obstetrics and Gynecology, School of MedicineThe IMPROVE study (NCT02408315) compared the efficacy and safety of vaginal and buccal administration of misoprostol for full-term, uncomplicated labor induction. This report compares the pharmacokinetics of misoprostol between vaginal and buccal routes. Women greater than or equal to 14 years of age undergoing induction of labor greater than or equal to 37 weeks gestation without significant complications were randomized to vaginal or buccal misoprostol 25 μg followed by 50 μg doses every 4 h. Misoprostol acid concentrations were determined using liquid chromatography-tandem mass spectrometry for the first 8 h in a subgroup of participants. A population pharmacokinetic model was developed using NONMEM. Plasma concentrations (n = 469) from 47 women were fit to a one-compartment nonlinear clearance model. The absorption rate constant (ka ) was dependent on both route and dose of administration: buccal 25 μg 0.724 (95% confidence interval, 0.54-0.92) h-1 ; 50 μg 0.531 (0.37-0.63) h-1 ; vaginal 25 μg 0.507 (0. 2-1. 4) h-1 ; and 50 μg 0.246 (0.103-0.453) h-1 . Relative bioavailability for vaginal compared to buccal route was 2.4 (1.63-4.77). There was no effect of body mass index or age on apparent clearance 705 (431-1099) L/h or apparent volume of distribution 632 (343-1008) L. The area under the concentration-time curve to 4 h following the first 25 μg dose of misoprostol was 16.5 (15.4-17.5) pg h/ml for buccal and 34.3 (32.5-36.1) pg h/ml for vaginal administration. The rate of buccal absorption was two times faster than that of vaginal, whereas bioavailability of vaginal administration was 2.4 times higher than that of buccal. Decreased time to delivery observed with vaginal dosing may be due to higher exposure to misoprostol acid compared to buccal.