Using partial area for evaluation of bioavailability and bioequivalence.

Assessment of bioavailability/bioequivalence generally relies on the comparison of rate and extent of drug absorption between products. Rate of absorption is commonly expressed by peak concentration (C(max)) and time to peak concentration (T(max)), although these parameters are indirect measures of absorption rate. Recognizing the importance of systemic exposure to drug efficacy and safety, FDA recommended that systemic exposure be better used for bioavailability/bioequivalence assessment. Apart from peak exposure and total exposure, FDA also recommended a new metric for early exposure that is considered necessary when a control of input rate is critical to ascertain drug efficacy and/or safety profile. The early exposure can be measured by truncating the area under the curve at T(max) of the reference product (PAUC(r,tmax)) or some designated early time after dosing. The choice of truncation is most appropriately based on PK/PD relationship or efficacy/safety data for the drug under examination. Compared with C(max), PAUC(r,tmax) has higher sensitivity in detecting formulation differences and may be more variable. If the metric is highly variable, the reference-scaling approach can be employed for bioequivalence evaluation. The partial area metric is useful in PK/PD characterization as well as in the evaluation of bioavailability, bioequivalence and/or comparability.

Opioid-Free Total Intravenous Anesthesia Improves Postoperative Quality of Recovery after Ambulatory Gynecologic Laparoscopy.

BACKGROUND: Gynecological laparoscopic surgery is commonly performed on an ambulatory basis under general anesthesia. The postoperative quality of recovery (QOR) should be considered one of the principal endpoints after ambulatory surgery. Total intravenous anesthesia (TIVA) with opioids is known to improve postoperative QOR after ambulatory surgery. However, opioids can be associated with an increased incidence of postoperative complications, which can affect postoperative QOR. The primary aim of this study was to compare the patient recovery using the QOR-40 at 24 h postoperative in ambulatory gynecological laparoscopy between opioid-free (OF) TIVA and opioid-based TIVA. SETTINGS AND DESIGN: A prospective, randomized, controlled, comparative study was conducted at the day surgery center. PATIENTS AND METHODS: Eighty females were included in the study. They were randomized into two equal groups: OF TIVA group with dexmedetomidine and propofol or opioid-based TIVA (O) group with fentanyl and propofol. The primary outcome was QOR-40 at 24 h postoperative, and the secondary outcomes were postoperative numerical rating scale (NRS), time to first rescue analgesia, number of rescue tramadol analgesia, and the incidence of postoperative nausea and vomiting. RESULTS: A statistically significant difference in total QOR-40 score at 24 h postoperative was observed between the groups (median [range] QOR-40 of 182.0 [164.0-192.0] in the OF TIVA group and 170.0 [156.0-185.0] in the O group; P = 0.03). OF group had significantly lower time to first rescue analgesia, maximum NRS pain scores, number of rescue tramadol analgesia, and ondansetron use. CONCLUSIONS: OF TIVA significantly improves postoperative QOR in patients undergoing ambulatory gynecological laparoscopic surgery.