The pathologic changes induced by Cis-platinum (II) diamminedichloride (CPDD) therapy in the kidneys are described in 12 patients with solid tumors and malignant lymphomas. According to dosage of CPDD the patients were divided into two groups: 1) low-dose group--.0.5-2 mg/kg daily, for 1 to 6 days; and 2) high-dose group--single injection of 3 or more mg/kg with concommitant mannitol-induced diuresis. Pathologic changes in the kidneys were essentially similar in both groups and consisted of focal acute tubular necrosis, affecting primarily the distal convoluted tubules and collecting ducts, dilatation of convoluted tubules, and formation of casts. These changes persisted as long as 29 days post CPDD therapy. In addition, the collecting ducts exhibited significant epithelial atypia. BUN and serum creatinine levels were elevated in both groups. The mean BUN/serum creatinine values were 54/2.2 mg/100 ml and 32/2.0 mg/100 ml for low and high-dose groups, respectively. Since the nephrotoxicity of CPDD is known to be dose-related, our findings suggest that mannitol-induced diuresis has considerably decreased the renal toxic damage of CPDD therapy in these patients.
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http://dx.doi.org/10.1002/1097-0142(197704)39:4<1362::aid-cncr2820390403>3.0.co;2-n | DOI Listing |
Clin Pharmacol Drug Dev
January 2025
Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, People's Republic of China.
Fluticasone propionate nasal spray is widely regarded as a first-line therapy for allergic rhinitis. To establish bioequivalence between the test and reference products of fluticasone propionate nasal spray, an open-label, randomized, single-dose, and 2-sequence crossover study was conducted on 84 healthy Chinese subjects under fasting conditions to determine the pharmacokinetic bioequivalence of the 2 products. Following a single-dose administration (200 µg) of fluticasone propionate nasal spray, pharmacokinetic parameters, including maximum plasma concentration, area under the concentration-time curve from administration to the last measurable concentration, and area under the concentration-time curve from administration to infinity, exhibited similarity between the 2 products, with 90% confidence intervals for the test/reference ratios falling within the bioequivalence range of 80%-125%.
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January 2025
Takeda Development Center Americas, Inc., Cambridge, MA, USA.
Mobocertinib is a kinase inhibitor designed to selectively target epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in non-small cell lung cancer. This drug-drug interaction study assessed the effect of multiple-dose administration of mobocertinib on the pharmacokinetics (PK) of midazolam, a sensitive cytochrome P450 3A substrate. Patients with locally advanced or metastatic non-small cell lung cancer refractory/intolerant to standard available therapy were enrolled.
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January 2025
Department of Pharmacometrics Modeling, A2-Ai LLC, Ann Arbor, MI, USA.
Certepetide (aka LSTA1 and CEND-1) is a novel cyclic tumor-targeting internalizing arginyl glycylaspartic acid peptide being developed to treat solid tumors. Certepetide is designed to overcome existing challenges in treating solid tumors by delivering co-administered anticancer drugs into the tumor while selectively depleting immunosuppressive T cells, enhancing cytotoxic T cells in the tumor microenvironment, and inhibiting the metastatic cascade. A population pharmacokinetic (PK) analysis was conducted to characterize the concentration-time profile of patients with metastatic exocrine pancreatic cancer receiving certepetide in combination with nab-paclitaxel and gemcitabine, and to investigate the effects of clinically relevant covariates on PK parameters.
View Article and Find Full Text PDFClin Pharmacol Drug Dev
December 2024
R&D Center, GEROPHARM, Saint-Petersburg, Russia.
During biosimilar drug development, conducting a clinical trial of biosimilar efficacy in patients may become necessary in the presence of residual uncertainty regarding the biosimilarity of the drugs. In the development of the biosimilar romiplostim GP40141, we aimed to use a model-based in silico clinical trial (ISCT) approach to optimize the planned biosimilar efficacy trial in patients with immune thrombocytopenia. The population pharmacokinetic/pharmacodynamic model for healthy volunteers was modified and validated to describe platelet dynamics in patients with immune thrombocytopenia.
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January 2025
Silver Creek Pharmaceuticals, Inc., South San Francisco, California, USA.
Apoptosis is a major driver of cell loss and infarct expansion in ischemic injuries such as acute ischemic stroke (AIS) and acute myocardial infarction (AMI). Insulin-like growth factor-1 (IGF-1) can mitigate cell death and potentiate recovery following acute ischemic injury, but short half-life and nonspecificity limit its therapeutic potential. Scp776 is an IGF-1 fusion protein designed to target damaged tissue and promote apoptosis escape and is in clinical development as an acute therapy for AIS and AMI.
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