Comparison of two biosimilarity studies of FKB327 with the adalimumab reference product: randomized phase 1 studies of single-blind, single-dose subcutaneous injection in healthy Japanese male participants

Background FKB327 has been developed as a biosimilar of the adalimumab reference product (RP). We compared the pharmacokinetics (PK), safety, and immunogenicity of FKB327 with those of the adalimumab RP after a single dose by subcutaneous (SC) injection in Japanese male participants. Methods Two randomized, single-blind, single-dose studies were conducted in healthy Japanese male participants to compare PK characteristics between FKB327 and the RP. Study 1 included 130 participants who were randomized in a 1:1 ratio to receive a subcutaneous injection of 40 mg of either FKB327 or the RP into the abdomen. In Study 2, another 130 subjects were randomized in a 1:1 ratio to receive either drug as in Study 1, but the drug administration site was changed to the thigh. The primary PK endpoints of both studies were area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) and maximum serum concentration; area under the concentration-time curve from time zero to 360 h was also evaluated as one of the primary endpoints in Study 1. Biosimilarity in terms of pharmacokinetics was determined if the 90% confidence interval of the mean difference in geometric mean ratio of all primary PK parameters was within the prespecified equivalence criteria (0.80–1.25). Immunogenicity and safety were also evaluated as secondary endpoints. Results The serum concentration-time profiles were comparable between the FKB327 and the RP treatment groups in both studies. Primary PK parameters were within the prespecified bioequivalence range in Study 2, although AUC0-t was slightly outside the upper side of the range in Study 1. No differences in safety profile were observed in these studies. The incidence of anti-drug antibodies (ADAs) and impact of ADAs on PK profile were similar among the treatment groups in both studies. Conclusion Biosimilarity between FKB327 and the RP after a single 40-mg SC injection was confirmed in healthy Japanese male participants by modifying the study design. Trial registration jRCT2071200058 (https://jrct.niph.go.jp/en-latest-detail/jRCT2071200058, https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2071200058) and jRCT2071200057 (https://jrct.niph.go.jp/en-latest-detail/jRCT2071200057, https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2071200057). Retrospectively registered 25/11/2020.

Bremelanotide for Treatment of Female Hypoactive Sexual Desire

Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD.

COMPARISON OF LOCAL METHYLCOBALAMINE INJECTION VERSUS LOCAL BUPIVACAINE INJECTION FOR THE TREATMENT OF ACUTE HERPETIC NEURALGIA

Objective: To compare the reduction in mean pain score with local Methylcobalamin injection versus local Bupivacaine injection in patients with acute herpetic neuralgia. Study Design: Quasi experimental study. Place and Duration of Study: Dermatology Outpatient Department, Pak Emirates Military Hospital, Rawalpindi, from Jun to Dec 2019. Methodology: Total 100 patients, having pain score more than 3, fulfilling the selection criteria were divided into two groups. Group A was treated with daily subcutaneous injection Bupivacaine, whereas Group B was treated with daily subcutaneous injection Methycobalamin at the site of neuralgia. Patients were followed up for 4 weeks. The pain score was noted. All the data was entered and analyzed on SPSS version 21. Results: In this study mean age of patients in group A was 43.82 ± 15.76 years and in group B was 44.76 ± 16.92 years. The mean visual analogue pain score at 4th week in the group A patients was 1.14 ± 0.32 and in group B was 1.90 ± 0.97. Statistically significant difference was found in group A (local Bupivacaine) with visual analogue score (VAS) at 4th week (pvalue=0.002). Conclusion: The local Bupivacaine injection showed significant reduction in mean pain score than local Methylcobalamin injection in patients with acute herpetic neuralgia.

Abdominal skin subcutaneous fat thickness over the gestational period in Korean pregnant women: a descriptive observational study

Purpose: Although insulin is usually injected into the abdominal subcutaneous fat, in pregnancy women tend to avoid abdominal injections due to concern about fetal damage. Prior studies have been limited to only measuring skin-subcutaneous fat thickness (S-ScFT) at one site at specific pregnancy points. This study aimed to measure S-ScFT across several abdominal sites and over the gestational period in Korean pregnant women. This can identify which site would be relatively safe for subcutaneous injection during pregnancy. Methods: Healthy women over 24 weeks of pregnancy in Korea were invited to voluntarily participate in this descriptive study. For the 142 women, S-ScFT of 12 sites in the abdomen were measured by ultrasound, several times over the pregnancy. Each incidence was treated as a case and a total of 262 cases were analyzed.Results: The mean S-ScFT during pregnancy was 1.14±0.47 cm (1.25±0.54 cm at 24+0–27+6 weeks; 1.17±0.48 cm at 28+0–31+6 weeks; 1.09+0.40 cm at 32+0–35+6 weeks; and 1.06±0.47 cm at 36+0–40 weeks of pregnancy). Most S-ScFT were thicker than 10 mm. But S-ScFTs in the lateral abdomen and some sites were suboptimal (<6 mm), especially in the pre-pregnancy underweight body mass index group, who had a high rate of suboptimal thickness (27.1% overall and 33.9% in the lateral side). Conclusion: The whole abdomen seems to be appropriate for subcutaneous injection in most pregnant Korean women, with a 4 to 5-mm short needle. However, for the lateral abdomen, making the skin fold might be needed for fetal safety.

Creatine Derivatives: Rapid Complete Relief of Pain by Topical or Transcutaneous Administration

Our research reveals that non-toxic creatine derivatives, especially N-acetyl-creatine ethyl ester, to be therapeutically effective on topical application or by superficial subcutaneous injection over sites of pain to rapidly alleviate or eliminate pain associated with various inflammatory conditions including arthritis, acute common headache, osteoarthritis, psoriatic arthritis, rheumatoid arthritis and various other pains associated with inflammation.

The Subcutaneous Injection of Organophosphate: A Case Report

Organophosphate (OP) poisoning is prevalent in developing countries. Toxicity occurs by voluntary injection, inhalation, and absorption. Self-injection is rare. The current case report describes a 61-y/o male with subcutaneous self-injected one cc OP poisoning presenting with delayed drowsiness, nausea, and vomiting. He was treated and presented a good clinical response to treatment with pralidoxime and had a successful recovery. Diagnosis of OP compound toxicity by the parenteral route is a challenge. By observing patients, the dose, and the time between poisoning until the time to start treatment, we can conclude different presentations and outcomes of OP poisoning.

Effect of Continuous Subcutaneous Injection of Insulin Analogues in Pregnant Women with Diabetes Mellitus Complicated with Ketoacidosis

Objective. To investigate the clinical effect of continuous subcutaneous injection of insulin analogues in pregnant women with diabetes mellitus complicated with ketoacidosis. Methods. A total of 92 pregnant patients with diabetes mellitus complicated with ketoacidosis from June 2014 to January 2021 were selected. All patients were randomly divided into an observation group and control group according to the method of random number. The control group received intravenous infusion of insulin, and the observation group received continuous subcutaneous infusion of quick-acting insulin analogues. The clinical effects of the two groups were observed. Results. The time needed to control blood glucose <13.8 mmol/L, the amount of insulin needed to control blood glucose <13.8 mmol/L, the time needed to correct DKA, and the amount of insulin needed to correct DKA in the observation group were significantly less than those in the control group ( P < 0.05 ). Compared with the control group, the average occurrence times of hypoglycemia, the length of stay, the total amount of insulin in hospital, and the total amount of insulin used during pregnancy in the observation group were significantly less than those in the control group ( P < 0.05 ). The values of SCr, CRP, BUN, arterial blood gas pH, and adiponectin in the two groups were significantly improved as compared with those before treatment, and the improvement in the observation group was significantly better than that in the control group ( P < 0.05 ). After treatment, the fasting blood glucose, 2-hour postprandial blood glucose, carbon dioxide binding capacity, and glycosylated hemoglobin in the experimental group were significantly better than those in the routine group, and the difference was statistically significant ( P < 0.05 ). Conclusion. Continuous subcutaneous injection of insulin analogues is effective in the treatment of diabetic patients with ketoacidosis, which can effectively improve blood glucose, carbon dioxide binding capacity, and glycosylated hemoglobin and accelerate the negative conversion of urinary ketone body. It is worth popularizing to reduce the occurrence of hypoglycemia and the dose of insulin and shorten the time of hospitalization.