Comparison of Vancomycin AUC24 Calculation Methods for Neonates and Infants.

Background And Objective: For neonates and infants receiving intermittent vancomycin infusions, the area under the concentration-time curve during 24 h (AUC24) is often estimated with Bayesian forecasting using one or more measured vancomycin concentrations. When practical peak and trough concentrations are measured at steady state, AUC24 can also be calculated with first-order steady-state equations for a one-compartment model (Sawchuk-Zaske method), but previously this method has been applied only for adults. The objective of this study was to compare AUC24 values obtained with the Sawchuk-Zaske method and two Bayesian models.

Comprehensive ocular and systemic pharmacokinetics of dexamethasone after subconjunctival and intravenous injections in rabbits.

Even though subconjunctival injections are used in clinics, their quantitative pharmacokinetics has not been studied systematically. For this purpose, we evaluated the ocular and plasma pharmacokinetics of subconjunctival dexamethasone in rabbits. Intravenous injection was also given to enable a better understanding of the systemic pharmacokinetics.

Breast milk oxycodone concentrations in mothers given oxycodone for post-Caesarean delivery pain management.

Aims: Both effective analgesia and early breastfeeding play an important role in maternal and neonatal well-being after Caesarean delivery. We studied controlled-release oxycodone tablet treatment for postoperative pain management and determined the excretion of oxycodone into breast milk.

Methods: Controlled-release oxycodone/naloxone 10/5-mg tablets (n = 21) or controlled-release oxycodone 10-mg tablets (n = 22) were administered to mothers twice a day for the first 3 days after elective Caesarean delivery as a part of multimodal analgesia.

Quantitative intravitreal pharmacokinetics in mouse as a step towards inter-species translation.

Although mouse models are widely used in retinal drug development, pharmacokinetics in mouse eye is poorly understood. In this study, we applied non-invasive in vivo fluorophotometry to study pharmacokinetics of intravitreal fluorescein sodium (molecular weight 0.38 kDa) and fluorescein isothiocyanate-dextran (FD-150; molecular weight 150 kDa) in mice.

Topical pharmacokinetics of brinzolamide suspensions in rabbits and variability analysis for sample size and design considerations.

Identifying critical attributes for complex locally acting ophthalmic formulations and establishing in vitro-in vivo correlations can facilitate selection of appropriate thresholds for formulation changes that reflect lack of impact on in vivo performance. In this study the marketed antiglaucoma product Azopt® (1% brinzolamide suspension) and five other brinzolamide formulations varying in particle size distributions and apparent viscosities were topically administered in rabbits, and their ocular pharmacokinetics was determined in multiple ocular tissues. Statistical evaluation with ANOVA showed no significant differences between the formulations in the peak drug concentration (C) in the aqueous humor and iris-ciliary body.

Central nervous system distribution of buprenorphine in pregnant sheep, fetuses and newborn lambs after continuous transdermal and single subcutaneous extended-release dosing.

Buprenorphine is used during pregnancy for the treatment of opioid use disorder. Limited data exist on the central nervous system (CNS) permeation and distribution, and on the fetal exposure to buprenorphine. The aim of our study was to determine the extent of buprenorphine distribution to CNS in the pregnant sheep, and their fetus at steady-state, and their newborn lambs postdelivery, using three different dosing regimens.

Quantitative pharmacokinetic analyses of anterior and posterior elimination routes of intravitreal anti-VEGF macromolecules using published human and rabbit data.

The purpose of this study was to evaluate the contribution of the anterior elimination route for four anti-vascular endothelial growth factor (anti-VEGF) macromolecules (aflibercept, bevacizumab, pegaptanib and ranibizumab) after intravitreal injection using published human and rabbit data and three previously described pharmacokinetic (PK) modeling methods. A PubMed search was used to identify published studies with concentration-time data. The data were utilized only if the intravitreally injected drugs were used as plain solutions and several criteria for a well-performed PK study were fulfilled.

Imaging, quantitation and kinetic modelling of intravitreal nanomaterials.

In this study, the intravitreal pharmacokinetics of nanomaterials were investigated in vivo in rats and rabbits. Impact of particle size and shape (spherical, longitudinal) on ocular particle distribution and elimination was investigated with fundus camera, optical coherence tomography and ocular fluorophotometry. Differently sized particles showed prolonged ocular retention and remarkable differences in vitreal elimination, but size dependence was consistent, suggesting that other features have influence on their vitreal kinetics.

Topical pharmacokinetics of dexamethasone suspensions in the rabbit eye: Bioavailability comparison.

Topical corticosteroids are used to treat inflammation of the anterior segment. Due to their low water-solubility, they are often formulated as suspensions, but ocular bioavailability of the suspensions is not known. Herein, ocular pharmacokinetics of dexamethasone in albino rabbits was investigated following intracameral administration of dexamethasone solution and topical administration of three commercial suspensions: Maxidex®, TobraDex®, and TobraDexST®.

Pharmacokinetics of Pullulan-Dexamethasone Conjugates in Retinal Drug Delivery.

The treatment of retinal diseases by intravitreal injections requires frequent administration unless drug delivery systems with long retention and controlled release are used. In this work, we focused on pullulan (≈67 kDa) conjugates of dexamethasone as therapeutic systems for intravitreal administration. The pullulan-dexamethasone conjugates self-assemble into negatively charged nanoparticles (average size 326 ± 29 nm).

MATERNAL AND FETAL BUPRENORPHINE PHARMACOKINETICS IN PREGNANT SHEEP DURING TRANSDERMAL PATCH DOSING: Buprenorphine pharmacokinetics in pregnant sheep.

Background: Buprenorphine is used in the opioid maintenance treatment for opioid dependent patients, including pregnant women. Despite the wide use, limited data exists on buprenorphine pharmacokinetics and fetal exposure during pregnancy. The aim of our study was to determine the buprenorphine pharmacokinetics during transdermal patch dosing to pregnant sheep and, to determine the extent of transplacental transfer of buprenorphine to the fetus.

Ocular pharmacokinetics of atenolol, timolol and betaxolol cocktail: Tissue exposures in the rabbit eye.

Quantitative understanding of pharmacokinetics of topically applied ocular drugs requires more research to further understanding and to eventually allow predictive in silico models to be developed. To this end, a topical cocktail of betaxolol, timolol and atenolol was instilled on albino rabbit eyes. Tear fluid, corneal epithelium, corneal stroma with endothelium, bulbar conjunctiva, anterior sclera, iris-ciliary body, lens and vitreous samples were collected and analysed using LC-MS/MS.

Intranasal Fentanyl for Intervention-Associated Breakthrough Pain After Cardiac Surgery.

Background: Cardiac bypass surgery patients have early postoperative interventions that elicit breakthrough pain. We evaluated the use of intranasal fentanyl for breakthrough pain management in these patients.

Methods: Multimodal analgesia (paracetamol 1 g three times a day, oxycodone 2-3 mg boluses with a patient-controlled intravenous pump) was used in 16 patients (age 49-70 years, weight 59-129 kg) after cardiac bypass surgery.

Pharmacokinetics of buprenorphine in pregnant sheep after intravenous injection.

Buprenorphine is a semi-synthetic opioid, widely used in the maintenance treatment for opioid-dependent pregnant women. Limited data exist on the pharmacokinetics of buprenorphine in pregnancy. We conducted a pharmacokinetic study to determine the pharmacokinetics of intravenous buprenorphine in pregnant sheep.

Pharmacokinetics of intravitreal macromolecules: Scaling between rats and rabbits.

Rats are widely used to study ocular drug responses, whereas rabbits are the most widely used preclinical model of ocular pharmacokinetics. Despite their wide use in evaluation of intravitreally injected drugs, translational information about pharmacokinetics and dose scaling between rats and rabbits is missing. In this study, we investigated intravitreal pharmacokinetics in rats and rabbits using non-invasive ocular fluorophotometry.

Extended Pharmacokinetic Model of the Intravitreal Injections of Macromolecules in Rabbits. Part 2: Parameter Estimation Based on Concentration Dynamics in the Vitreous, Retina, and Aqueous Humor.

Purpose: To estimate the diffusion coefficients of an IgG antibody (150 kDa) and its antigen-binding fragment (Fab; 50 kDa) in the neural retina (D) and the combined retinal pigment epithelium-choroid (D) with a 3-dimensional (3D) ocular pharmacokinetic (PK) model of the rabbit eye.

Methods: Vitreous, retina, and aqueous humor concentrations of IgG and Fab after intravitreal injection in rabbits were taken from Gadkar et al. (2015).

Comprehensive Ocular and Systemic Pharmacokinetics of Brinzolamide in Rabbits After Intracameral, Topical, and Intravenous Administration.

Brinzolamide is a topical carbonic anhydrase inhibitor which reduces the production of aqueous humor in the ciliary body, thereby reducing intra-ocular pressure. It is formulated as an ophthalmic suspension. The pharmacokinetics of ocular suspensions is not well understood.

Topical ocular pharmacokinetics and bioavailability for a cocktail of atenolol, timolol and betaxolol in rabbits.

Ocular bioavailability after eye drops administration is an important, but rarely determined, pharmacokinetic parameter. In this study, we measured the pharmacokinetics of a cocktail of three beta blockers after their topical administration into the albino rabbit eye. Samples from aqueous humour were analysed with LC-MS/MS.

Bioavailability of oxycodone by mouth in coronary artery bypass surgery patients - a randomized trial.

Objective: Pain after coronary artery by-pass (CAB) surgery is severe. Analgesic administration by mouth is unreliable until after gastrointestinal function has recovered. We evaluated the bioavailability of oxycodone co-administered with naloxone by mouth in patients after CAB surgery using either a conventional extracorporeal circulation (CECC) or off-pump surgery (OPCAB).

Physiologically based pharmacokinetic modelling of oxycodone drug-drug interactions.

Oxycodone is an opioid analgesic with several pharmacologically active metabolites and relatively narrow therapeutic index. Cytochrome P450 (CYP) 3A4 and CYP2D6 play major roles in the metabolism of oxycodone and its metabolites. Thus, inhibition and induction of these enzymes may result in substantial changes in the exposure of both oxycodone and its metabolites.

Ocular Intracameral Pharmacokinetics for a Cocktail of Timolol, Betaxolol, and Atenolol in Rabbits.

The mechanisms of drug clearance from the aqueous humor are poorly defined. In this study, a cocktail approach was used to simultaneously determine the pharmacokinetics of three β-blocker agents after intracameral (ic) injection into the rabbit eyes. Aqueous humor samples were collected and analyzed using LC-MS/MS to determine drug concentrations.

Distribution of Small Molecular Weight Drugs into the Porcine Lens: Studies on Imaging Mass Spectrometry, Partition Coefficients, and Implications in Ocular Pharmacokinetics.

Lens is the avascular tissue in the eye between the aqueous humor and vitreous. Drug binding to the lens might affect ocular pharmacokinetics, and the binding may also have a pharmacological role in drug-induced cataract and cataract treatment. Drug distribution in the lens has been studied in vitro with many compounds; however, the experimental methods vary, no detailed information on distribution between the lens sublayers exist, and the partition coefficients are reported rarely.

Analgesic efficacy and pharmacokinetics of epidural oxycodone in pain management after gynaecological laparoscopy-A randomised, double blind, active control, double-dummy clinical comparison with intravenous administration.

Aims: Early pain after laparoscopy is often severe. Oxycodone is a feasible analgesic option after laparoscopy, but there are sparse data on epidural administration. The aim was to evaluate the analgesic efficacy and pharmacokinetics of a single dose of epidural oxycodone as a part of multimodal analgesia after gynaecological laparoscopy.