The growth of the vocal tract (VT) is known to be non-uniform insofar as there are regional differences in anatomic maturation. This study presents quantitative anatomic data on the growth of the oral and pharyngeal portions of the VT from 605 imaging studies for individuals between birth and 19 years. The oral (horizontal) portion of the VT was segmented into lip-thickness, anterior-cavity-length, oropharyngeal-width, and VT-oral; and the pharyngeal (vertical) portion of the VT into posterior-cavity-length, and nasopharyngeal-length. The data were analyzed to determine growth trend, growth rate and growth type (neural or somatic). Findings indicate differences in the growth trend of segments/variables analyzed, with significant sex differences for all variables except anterior-cavity-length. While the growth trend of some variables display prepubertal sex differences at specific age ranges, the importance of such localized differences appears to be masked by overall growth rate differences between males and females. Finally, assessment of growth curve type indicates that most VT structures follow a combined/hybrid (somatic and neural) growth curve with structures in the vertical plane having a predoMinantly somatic growth pattern. these data on the non-uniform growth of the vocal tract reveal anatomic differences that contribute to documented acoustic differences in prepubertal speech production.

Inhibition of hepatic transporters such as organic anion transporting polypeptides (OATPs) 1B can cause drug-drug interactions (DDIs). Determining the impact of perpetrator drugs on the plasma exposure of endogenous substrates for OATP1B could be valuable to assess the risk for DDIs early in drug development. As OATP1B orthologs are well conserved between human and monkey, we assessed in cynomolgus monkeys the endogenous OATP1B substrates that are potentially suitable to assess DDI risk in humans. The effect of rifampin (RIF), a potent inhibitor for OATP1B, on plasma exposure of endogenous substrates of hepatic transporters was measured. From the 18 biomarkers tested, RIF (18 mg/kg, oral) caused significant elevation of plasma unconjugated and conjugated bilirubin, which may be attributed to inhibition of cOATP1B1 and cOATP1B3 based on in vitro to in vivo extrapolation analysis. To further evaluate whether cynomolgus monkeys are a suitable translational model to study OATP1B-mediated DDIs, we determined the inhibitory effect of RIF on in vitro transport and pharmacokinetics of rosuvastatin (RSV) and atorvastatin (ATV). RIF strongly inhibited the uptake of RSV and ATV by cOATP1B1 and cOATP1B3 in vitro. In agreement with clinical observations, RIF (18 mg/kg, oral) significantly decreased plasma clearance and increased the area under the plasma concentration curve (AUC) of intravenously administered RSV by 2.8-and 2.7-fold, and increased the AUC and maximum plasma concentration of orally administered RSV by 6-and 10.3-fold, respectively. In contrast to clinical findings, RIF did not significantly increase plasma exposure of either intravenous or orally administered ATV, indicating species differences in the rate-limiting elimination pathways.

Purpose-The anatomic origin for prepubertal vowel acoustic differences between males and females remains unknown. The purpose of this study is to examine developmental sex differences in vocal tract (VT) length and its oral and pharyngeal portions.Method-Nine VT variables were measured from 605 imaging studies (MRI and CT) between birth and 19 years. Given sex differences in growth rate ), assessment of sex differences was done using a localized comparison window of 60 months. Analysis entailed applying this comparison window first to four discrete age cohorts, followed by a progressive assessment where this comparison window was moved in one month increments from birth across all ages.Results-Findings document significant postpubertal sex differences in both the oral and pharyngeal portions of the VT. Also, periods of significant prepubertal sex differences in the oral region first, followed by segments in the pharyngeal region. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptConclusions-Assessment of developmental sex differences using localized age ranges is effective in unveiling sex differences that growth rate differences may conceal. Findings on the presence of prepubertal sex differences in the oral region of the VT may clarify in part the anatomic basis of documented prepubertal acoustic differences.

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