A comparative pharmacokinetic study of intravenous and intramuscular midazolam in patients with epilepsy

The pharmacokinetics of midazolam, a water soluble 1,4-benzodiazepine, has been studied in 12 patients (11 male, 1 female; age range 19–57 years) with epilepsy. All patients were taking hepatic enzyme inducing antiepileptic drugs (AEDs) on a regular basis. Midazolam (5 mg) was administered intravenously and 1 week later midazolam was administered intramuscularly, the dose used being dependent on the sedative response to the intravenous dose (10 mg, N = 2; 7 mg, N = 8; 5 mg, N = 2). Serial blood samples were collected at timed intervals for 5–7 h. After intravenous administration initial distribution was rapid with a mean half-life (t¹/2) of 0.06 ± 0.03 h followed by a terminal half-life (t¹/2β or γ) of 1.5 ± 0.3 h. Volume of distribution was 0.62 ± 0.27 1/kg. After intramuscular administration midazolam was rapidly absorbed with peak serum concentrations achieved at 25 ± 23 min. Two patients showed delayed absorption. Mean terminal half-life was 2.8 ± 1.7 h. The absolute bioavailability of intramuscular midazolam was calculated in 11 patients as 87 ± 18%. Sedation was rapid (< 1–2 min) but transient (7–75 min) after intravenous and slower (2–30 min) and for a longer period (20–120 min) after intramuscular administration. Since intravenous administration of AEDs including diazepam is not always feasible in status epilepticus there are obvious advantages in having an effective intramuscular formulation. Our data suggest that midazolam may be such a drug.     

Human leukocyte antigens antibodies after lung transplantation: Primary results of the HALT study

Donor‐specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA. The median DSA mean fluorescence intensity (MFI) was 3197. We identified a significant association between the Lung Allocation Score and the development of DSA (HR = 1.02, 95% CI: 1.001‐1.03, P = .047) and a significant association between DSA with an MFI ≥ 3000 and acute cellular rejection (ACR) grade ≥ A2 (HR = 2.11, 95% CI: 1.04‐4.27, P = .039). However, we did not detect an association between DSA and survival. We conclude that DSA occur frequently early after lung transplantation, and most target class II HLA. DSA with an MFI ≥ 3000 have a significant association with ACR. Extended follow‐up is necessary to determine the impact of DSA on other important outcomes.     

Co-existing granular cell tumor and adenocarcinoma of the lung: a case report and review of the literature

Granular cell tumor (GCT) of the lung is a rare tumor, constituting less than 10% of all GCTs. It is a multicentric tumor and infiltrates into adjoining tissue, but malignant GCT of the lung has not been reported. Diagnosis is usually obtained with bronchoscopic biopsy. Treatment options include bronchoscopic extirpation, laser therapy, and sleeve resection. We present a case of GCT co-existing with adenocarcinoma of the lung and review the literature.