Issue Information

http://ift.tt/2fTFIdl

Population Pharmacokinetic Meta-Analysis of Ramucirumab in Cancer Patients

Aim

Ramucirumab is a human IgG1 monoclonal antibody that specifically binds vascular endothelial growth factor receptor-2 (VEGFR-2) and blocks binding of VEGF-A, VEGF-C, and VEGF-D. The objective of the analysis was to characterize the clinical pharmacology profile of ramucirumab using a population pharmacokinetic approach.

Methods

A total of 1639 patients with 6427 serum concentrations from 11 Phase 1b, 2, and 3 clinical trials in patients with various cancer indications were included in the analysis. Ramucirumab was administered as an i.v. infusion over 1 hour at 8 mg kg^-1 every 2 weeks or 10 mg kg^-1 every 3 weeks. A series of pharmacostatistical models were developed to describe the concentration data. The best model was used to evaluate patient factors for their effect on ramucirumab pharmacokinetics.

Results

The pharmacokinetics of ramucirumab were well characterized by a two-compartment model. Mean population estimates of clearance (CL), volume of distribution (V_ss), and half-life (t_1/2) for a typical 68-kg patient were 0.0148 l h^-1, 5.30 l, and 13.4 days, respectively. A modest relationship was observed between body weight and ramucirumab disposition; CL and V₁ increased with body weight. No other patient characteristics were shown to influence the disposition of ramucirumab in this patient population.

Conclusions

The final model adequately described the concentration-time profile of ramucirumab in patients with a range of cancer indications. The model confirmed that a weight-normalized dosing regimen is appropriate for ramucirumab therapy. Dose adjustment was not required for patients with mild to moderate renal impairment or mild hepatic impairment.

http://ift.tt/2wZr6gl

Response to Editorial, midwifery education

Publication date: Available online 18 August 2017
Source:Women and Birth
Author(s): Kairan A. Meek, Rosannah L. Skufca




http://ift.tt/2vMnjV7

Priapism due to essential thrombocythaemia: a rare causation

Priapism is rarely caused by essential thrombocytosis, a disorder characterised by increased number of megakaryocytes. We report a case of a 21-year-old man who presented with priapism and on investigation was found to have essential thrombocytosis as the cause.

http://ift.tt/2ie6myd

Renal cell carcinoma presenting as a cutaneous horn and nodules on the gingiva and scalp

A 63-year-old man presented with a pulsatile cutaneous horn on the nose and multiple angiomatous nodules on the gingiva and scalp, which appeared over 2 months. He had severe hypercalcaemia, lytic lesions in multiple bones and acute kidney injury. Excision biopsy from the gingival nodule showed a clear cell neoplasm. The bone marrow showed atypical cells with similar morphology. Imaging showed a 7 cmx7.5 cm mass at the upper pole of the left kidney with metastases to the bones, liver and lung. Immunohistochemistry was consistent with metastatic renal cell carcinoma. Renal cell carcinoma presenting as a cutaneous horn is extremely rare and to the best of our knowledge only one other case was found in the literature. There was visible regression in the size of the cutaneous horn and nodules following initiation of pazopanib therapy. However, he succumbed to his illness a month later.

http://ift.tt/2fTZEN4

Bilateral optic disc coloboma

Description

A 5-month-old male child was brought with the history of right-sided corneal opacity noticed for the past 2 months. The baby was immunised until now with an uneventful antenatal and peripartum history. Ocular examination showed normal sized cornea having a paracentral nebular opacity along the inferior and nasal aspect without any discharge or significant exposure keratopathy. The baby was able to fix at the light with each eye separately, the anterior chamber in both the eyes was of normal depth having a clear lens and retinal examination showed a well-defined posteriorly excavated area along the inferior portion of the optic disc in both the eyes. Sleeping intraocular pressures were 10 and 12 mm Hg in right eye and left eye, respectively. Posterior segment B-scan ultrasound showed a well-defined symmetric excavation along the inferior aspect of the optic disc in both the eyes with an axial length of 20 mm...

http://ift.tt/2ie6iyt

Idiopathic spontaneous lesser sac haematoma: a perplexing case of abdominal apoplexy

A 37-year-old woman presented with a 3-hour history of back pain, nausea and vomiting and an episode of syncope. A fluid collection in the lesser sac was detected on ultrasound and CT scan. Emergency laparoscopy and subsequent laparotomy were performed and a large blood clot was evacuated from the lesser sac. No identifiable source or predisposition to bleeding was found. She made a full recovery postoperatively. There are few reported cases of spontaneous intraperitoneal haemorrhage. In a third of cases, there is no identifiable source of bleeding. Unfortunately, patients present late with non-specific symptoms and a prompt diagnosis is difficult to make. The case reiterates the importance of awareness of lesser sac haematoma formation; an unusual clinical entity with a high morbidity and mortality rate. A high index of suspicion, radiological adjuncts and appropriate surgical intervention, especially in unstable patients, is essential for a good outcome.

http://ift.tt/2fU4D02