Stability of extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution

Disclaimer In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose To advance the implementation of consciousness-promoting therapies in patients with acute disorders of consciousness, the availability of potential therapeutic agents in formulations suitable for administration in hospitalized patients in the presence of complex comorbid conditions is paramount. The purpose of this study is to evaluate the long-term stability of extemporaneously prepared preservative-free methylphenidate hydrochloride (HCl) 5 mg/mL intravenous solution for experimental use. Methods A methylphenidate 5 mg/mL solution was prepared under proper aseptic techniques with Methylphenidate Hydrochloride, USP, powder mixed in sterile water for solution. Methylphenidate HCl 5 mg/mL solution was sterilized by filtration technique under USP <797>–compliant conditions. Samples were stored refrigerated (2-8°C) and analyzed at approximately days 1, 30, 60, 90, 180, and 365. At each time point, chemical and physical stability were evaluated by visual inspection, pH measurement, membrane filtration procedure, turbidometric or photometric technique, and high-performance liquid chromatography analysis. Results Over the 1-year study period, the samples retained 96.76% to 102.04% of the initial methylphenidate concentration. There was no significant change in the visual appearance, pH level, or particulate matter during the study period. The sterility of samples was maintained and endotoxin levels were undetectable throughout the 1-year stability period. Conclusion Extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution was physically and chemically stable at 32, 61, 95, 186, and 365 days when stored in amber glass vials at refrigerated temperatures (2-8°C).

Pharmacokinetics and Bioequivalence of Isavuconazole Administered as Isavuconazonium Sulfate Intravenous Solution via Nasogastric Tube or Orally in Healthy Subjects

For critically ill patients with invasive fungal infections, administration of isavuconazonium sulfate (ISAVUSULF) via nasogastric (NG) tube can be an alternative route of drug administration. This was a randomized, open-label, 2-period, 2-sequence single-dose crossover study comparing single doses of 372 mg ISAVUSULF intravenous (IV) solution via NG tube (test formulation) to 372 mg ISAVUSULF capsules for oral administration (reference formulation) in healthy male and female subjects. A single dose of ISAVUSULF was administered under fasting conditions on Day 1 of each period, with a washout of 30 days between each period. Pharmacokinetic (PK) samples were collected predose through Day 21. Standard safety and tolerability assessments were conducted in each period. The analysis of variance estimate of the study population demonstrates that the isavuconazole IV NG tube administration Geometric least squares (LS) mean values of the observed maximum concentration (C max ), area under the plasma concentration–time curve (AUC) to the last measurable concentration (AUC last ), AUC to time infinity (AUC inf ), and AUC from start of dosing to 72 hours (AUC 72 ) were 105.3%, 97.6%, 99.3% and 97.8%, respectively, of the corresponding oral administration values. The Geometric LS mean ratio and 90% confidence intervals for the PK parameters were completely contained within the prespecified limits of 80% to 125%. There were no deaths or serious adverse events that led to the withdrawal of treatment during the study. The study met its primary endpoint of bioequivalence between the two routes of administration. Both routes of administration were well tolerated.

Correcting hypophosphataemia in a paediatric patient with Sanjad–Sakati syndrome through a single oral dose of potassium phosphate intravenous solution

Sanjad–Sakati syndrome is an autosomal recessive disorder that is quite common in Kuwait. Among a wide range of complications in Sanjad–Sakati syndrome patients is the vulnerability to infections and subsequent hypophosphataemia. Hypophosphataemia is a metabolic alteration that contributes to numerous consequences such as cardiac arrhythmia. Therefore, if hypophosphataemia is left unresolved, it may culminate in death. A 20-month-old boy of 2.5 kg body weight diagnosed with Sanjad–Sakati syndrome was initially admitted to the paediatric intensive care unit after recovering from COVID-19, and then shifted to the general ward. He was diagnosed with recurrent pneumonia and urinary tract infection. After 9 days, the patient showed severe hypophosphataemia with serum phosphate concentration reaching 0.33 mmol/L. Despite the availability of potassium phosphate intravenous solution, it was difficult to administer potassium phosphate intravenously because of the small body size and low body weight of the patient. Therefore, 0.6 mL potassium phosphate containing 2.4 mEq of potassium and 5.3 mEq of phosphate was administered through a nasogastric tube. The patient showed rapid response after a single dose through the nasogastric tube. Such an intervention in Sanjad–Sakati syndrome patients shows possible advantages of shifting drug administration from intravenous to oral route that includes a convenient route of administration, whether in the intensive care unit or in the general ward. Moreover, shifting drug administration from the intravenous to oral route overcomes the risk of cannula-induced infection and reduces nurses’ workload.

The effectiveness of “Iodozol” in combination therapy in the treatment of postpartum vulvitis in goats

In the nosology of obstetric pathology of goats a special place is occupied by postpartum lesions of the genitals by pathogenic microflora, of which the lion's share are postpartum vulvitis. The aim of the study was to test a new treatment regimen for postpartum vulvitis in goats and to study the therapeutic efficacy of the drug “Iodozol”, “Celexib” and “Dextrodev 50” in this pathology. Clinical and anamnestic data showed that the symptoms of postpartum vulvitis of goats were characterized by inflammatory edema, high pain, local fever, impaired tissue integrity, hematomas and discharge from the genital tract. Microbiological studies of secretions from the genitals revealed the presence of E. coli, S. aureus, less often – S. saprophyticus and E. faecalis. High resistance of microorganisms to fluoroquinolones and penicillins is noted. E. coli was sensitive to only 35.7 % of antimicrobial drugs, including ceftriaxone, ceftiofur, and iodine. S. aureus is sensitive to 49.9 % of antimicrobial drugs, including ceftriaxone, cephalexin, gentamicin, ceftiofur, iodine (highest sensitivity) and chlorhexidine. S. saprophyticus was insensitive to a number of antibiotics (oxytetracycline, gentamicin, etc.), except iodine. Taking into account microbiological researches the complex scheme of treatment of postpartum vulvitis at goats is developed. Evaluation of the effectiveness of complex therapy of this pathology in animals showed that treatment with “Iodozole”, “Celexib” and “Dextrodev 50” in a short time eliminates inflammatory symptoms (pain, infiltration, redness, discharge). At the end of the course of treatment in the blood was observed an increase in hemoglobin concentration by 13.7 %, a decrease in the number of erythrocytes by 1.7 and leukocytes by 2.2 times compared with treatment. The topical intrauterine drug “Iodozol”, a non-steroidal injectable drug “Celexib”, has been found to have a broad spectrum of antimicrobial activity, and is effective and safe to use. The drugs have an anti-edematous and analgesic effect, and symptomatic treatment with intravenous solution “Dextrodev 50” is a mandatory component of complex therapy and is aimed at replenishing the body with nutrients, as well as helps to neutralize and remove toxins from the body. Further research will be to study the clinical efficacy and develop regulations for the use of this scheme in vulvitis and cervicitis of other ruminants.

Case Report of Successful IVF with Pregnancy of a 46 Year Old Lady after 12 Years Trials and 10 failed IVFs

Background: In this study, we indicate the importance of a case, where specific diagnostic tests such as NK level, NK endometrial cells, NK activity, embryotoxicity (ETA), and PLA (platelet leukocyte aggregates) were used for investigating infertile women with many failed IVFs. Case presentation: We describe a very important case of unexplained infertility, where a 46 year old lady managed finally to get pregnant after 12 years of consecutive trials and 10 failed IVFs. Our center tested her for all 3 NK markers, ETA, and Vitamin D3, TSH, and PLA, which are essential for positive pregnancy. The lady was treated with intravenous solution of intralipid after the high NK result. She was administered with two dosages and then performed embryo transfer where after 10 days she received the positive pregnancy test result. Conclusion: The high evaluation of immune status based on the specific tests of NK panel (all 3 markers), ETA, and PLA can save time and money for couples that have attempted several embryo transfers in IVF centers with unsuccessful pregnancies. Also, the targeted individualized treatment of the couple can significantly increase the chances for successful pregnancy.

Stability of Extemporaneously Prepared Preservative-Free Methylphenidate 5 mg/mL Intravenous Solution

Purpose: To advance the implementation of consciousness-promoting therapies in patients with acute disorders of consciousness, the availability of potential therapeutic agents in formulations suitable for administration in hospitalized patients in the presence of complex comorbid conditions is paramount. The purpose of this study is to evaluate the long-term stability of extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution. Methods: A methylphenidate 5 mg/mL solution was prepared under proper aseptic techniques with Methylphenidate HCl USP powder mixed in sterile water for solution. Methylphenidate HCl 5 mg/ml solution was sterilized by filtration technique under USP <797> compliant conditions. Samples were stored refrigerated (2-8C) and analyzed at approximately day 1, 30, 60, 90, 180, and 365. At each time point, chemical and physical stability was evaluated by visual inspection, pH measurement, membrane filtration procedure, turbidometric or photometric technique, and high-performance liquid chromatography (HPLC) analysis. Results: Over the 1 year study period, the sample retained 96.76-102.04% of initial methylphenidate concentration. There was no significant change in the visual appearance, pH level or particulate matter during the study period. The sample maintained bacterial and fungi sterility, and endotoxin levels were undetectable throughout the 1 year stability period. Conclusions: Extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution was physically and chemically stable for up to 365 days when stored in amber glass vials at refrigerated temperatures (2-8C).

Use of locally prepared peritoneal dialysis (PD) fluid for acute PD in children and infants in Africa

Background: In less well-resourced countries, the high cost of commercially available peritoneal dialysis (PD) fluid limits its use. The major concerns regarding bedside-prepared PD fluid is peritonitis as well as electrolyte disorders. The aim of this study was to review our experience with the use of PD fluids prepared at the bedside using the intravenous infusion solution Balsol (Fresenius Kabi). Methods: This was a retrospective review of all patients who received PD for acute kidney injury (AKI) using a bedside-prepared PD solution adapted from the intravenous solution Balsol in our intensive care unit. Results: In total, 49 cases of acute PD were performed. Of the 49 children, 21 (43%) were male. The ages of the patients ranged from newborn to 10.2 years (median 0.33 years). The weight of children ranged from 1.3 kg to 50 kg (median 4.1 kg). The type of PD catheters used: Cook catheters, 41 patients; Kimal peel-away, 10 patients; and surgical inserted Tenckhoff type of catheter, 2 patients. The duration of PD was 1–17 days (median 3 days) Complications included peritonitis in 2 of 49 patients and blocked catheter in 6 of 49 patients. There were no electrolyte disturbances as a result of the PD. Overall survival was 43% of patients. Conclusions: Locally prepared PD solutions at the bedside adapted from intravenous solutions can be used safely and effectively. This has important relevance for centres in less well-resourced countries, where commercially produced PD fluid is not available for the management of AKI.