Interaction between buprenorphine and norbuprenorphine in neonatal opioid withdrawal syndrome.

Buprenorphine (BUP) is the preferred treatment for opioid use disorder during pregnancy but can cause neonatal opioid withdrawal syndrome (NOWS). Norbuprenorphine (NorBUP), an active metabolite of BUP, is implicated in BUP-associated NOWS. We hypothesized that BUP, a low-efficacy agonist of mu opioid receptors, will not antagonize NorBUP, a high-efficacy agonist of mu opioid receptors, in producing NOWS.

The brain-penetrant cell-cycle inhibitor p28 sensitizes brain metastases to DNA-damaging agents.

Background: Brain metastases (BMs), the most common tumors of the central nervous system, are life-threatening with a dismal prognosis. The major challenges to developing effective treatments for BMs are the limited abilities of drugs to target tumors and to cross the blood-brain barrier (BBB). We aimed to investigate the efficacy of our therapeutic approach against BMs in mouse models that recapitulate the clinical manifestations of BMs.

Nontoxic Tumor-Targeting Optical Agents for Intraoperative Breast Tumor Imaging.

Precise identification of the tumor margins during breast-conserving surgery (BCS) remains a challenge given the lack of visual discrepancy between malignant and surrounding normal tissues. Therefore, we developed a fluorescent imaging agent, ICG-p28, for intraoperative imaging guidance to better aid surgeons in achieving negative margins in BCS. Here, we determined the pharmacokinetics (PK), biodistribution, and preclinical toxicity of ICG-p28.

metabolic biomodulation of irinotecan to increase potency and reduce dose-limiting toxicity by inhibition of SN-38 glucuronide formation.

Objectives: Colorectal cancer continues to have one of the highest incidents of occurrence with a rising rate of diagnosis among people under the age of 50. Chemotherapy with irinotecan results in severe gastrointestinal dose-limiting toxicity that is caused by the glucuronidated form of the active metabolite (SN-38G). This study evaluates herbal compounds and analogs to biomodulate the metabolism of IR to decrease dose-limiting toxicity while increasing the amount of the active metabolite.

Pharmacokinetic and Histopathologic Study of an Extended-Release, Injectable Formulation of Buprenorphine in Sprague-Dawley Rats.

A novel buprenorphine (BUP) extended-release formulation (BUP-XR) produced as a lipid-encapsulated, low viscosity BUP suspension for SC injection to control pain was evaluated for pharmacokinetics and safety in Sprague-Dawley rats given either 0.65 mg/kg (low dose) or 1.30 mg/kg (high dose).

Preclinical pharmacokinetics, metabolism, and toxicity of azurin-p28 (NSC745104) a peptide inhibitor of p53 ubiquitination.

Purpose: Characterize the preclinical pharmacokinetics, metabolic profile, multi-species toxicology, and antitumor efficacy of azurin-p28 (NSC 745104), an amphipathic, 28 amino acid fragment (aa 50-77) of the copper containing redox protein azurin that preferentially enters cancer cells and is currently under development for treatment of p53-positive solid tumors.

Methods: An LC/MS/MS assay was developed, validated, and applied to liver microsomes, serum, and tumor cells to assess cellular uptake and metabolic stability. Pharmacokinetics was established after administration of a single intravenous dose of p28 in preclinical species undergoing chronic toxicity testing.

A novel and rapid LC/MS/MS assay for bioanalysis of Azurin p28 in serum and its pharmacokinetics in mice.

Azurin p28 (NSC745104) is a 28 amino acid peptide fragment that inhibits proliferation of human solid and hematological malignancies in vitro and in vivo by reducing proteasomal degradation of oncogene p53. The present study aimed at developing a novel and fast liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the bioanalysis of p28 in mouse serum, and determining Azurin p28 stability and pharmacokinetics in mice after full method validation. Both Azurin p28 and its internal standard MP-1 were separated and extracted from serum by using perchloric acid (7%, v/v) without time-consuming reconstitution.

Pharmacokinetics and pharmacodynamics of Phor21-betaCG(ala), a lytic peptide conjugate.

Phor21-betaCG(ala), a 36-amino acid peptide comprised of a lytic peptide (Phor21) conjugated to a modified 15-amino acid segment of the beta-chain of chorionic gonadotropin (betaCG(ala)), selectively kills cancer cells that over-express luteinizing hormone/chorionic gonadotropin (LH/CG) receptors by disrupting cellular membrane structure. These studies were designed to further characterize its in-vitro inhibition and in-vivo destruction of prostate cancer cells, biostability and pharmacokinetics to determine its pharmacokinetic and pharmacodynamic profile. Inhibitory effects of Phor21-betaCG(ala) were tested in PC-3 and Caco-2 cells as well as in nude mice bearing PC-3 cells transfected with the luciferase gene (PC-3.