Rectal Drug Delivery to Paediatric Population

Despite its unpopularity, the rectal route of paediatric drug administration remains of interest especially in pre-school children as it can overcome some drug delivery challenges with oral and parenteral routes. Few studies have been conducted on the use and acceptability of traditional rectal dosage forms (i.e., suppositories, enemas and gels) in different parts of the world. It showed that barrier to adoption could be linked with poor knowledge, little information and understanding of this administration modality. Reformulation for the rectal delivery of drugs intended for oral and/or parenteral administration that do not reach their full potential, was explored by a study at University College London. The top 3 candidates were Azithromycin, Amodiaquine and Raltegravir. Little rectal delivery innovation has occurred but topics such as acceptability and use of rectal drug delivery; types of rectal dosage forms and reformulation considerations are discussed presently in order to raise awareness around the need to modernise rectal dosage forms this to achieve the full potential for successful reformulation.

Interferon-λ Improves the Efficacy of Intranasally or Rectally Administered Influenza Subunit Vaccines by a Thymic Stromal Lymphopoietin-Dependent Mechanism

Previous work showed that interferon-λ (IFN-λ) can trigger the synthesis of thymic stromal lymphopoietin (TSLP) by specialized epithelial cells in the upper airways of mice, thereby improving the performance of intranasally administered influenza vaccines. Here we demonstrate that protein-only influenza vaccines containing either IFN-λ or TSLP boosted antigen-specific IgG1 and IgA responses and enhanced the resistance of mice to influenza virus challenge, irrespective of whether the vaccines were applied via the intranasal or the rectal route. TSLP receptor deficiency negatively influenced vaccine-induced antiviral immunity by impairing the migration of dendritic cells from the airways to the draining lymph nodes of immunized mice, thereby restraining follicular helper T cell and germinal center B cell responses. As previously observed during intranasal vaccination, the adjuvant effect of IFN-λ on a rectally administered influenza vaccine was no longer observed when TSLP receptor-deficient mice were used for immunization, highlighting the central role of the IFN-λ/TSLP axis for vaccine-induced antiviral immunity in the mucosa.

To compare efficacy of Diclofenac by intramuscular route and rectal route in post surgical pain.

Objective: This study was carried out in Lahore General Hospital, Lahore to test the results of Intramuscular vs Suppository form of Diclofenac Sodium on the severity of post-surgical pain in patients who underwent Cesarean delivery under Subarachnoid Block. Study Design: Randomized Study. Setting: Lahore General Hospital, Lahore. Period: April 2019 to September 2019. Material & Methods: This was a double-blind run on 100 patients who underwent for cesarean delivery irrespective of any indication for the procedure. The pain sufferers had been randomly divided into 2 groups. The group A: who received Diclofenac Sodium in the form of suppository and Group B: who received intramuscular Diclofanec Sodium? The pain severity was assessed using VAS scale at categorically unique times. Data was then analyzed using SPSS 23 version and the results were compiled in the form of mean and percentage. Results: The mean age (Years) of patients was (25.27±6.07). There was a big statistical difference between the 2 groups regarding pain score after the intervention (p=0.018). Conclusion: To reaffirm the effectiveness of Diclofenac for Post-Caesarean section, the physique part (Suppository) is established to hold advantages over the contractile organ (muscles).

Pharmacokinetic Characteristics of a Nifedipine and Lidocaine Fixed Combination in the Form of Rectal Cream: Two Decades Data Analysis

The creation of medicines' fixed combinations from compounds with complementary effects is one of the most popular directions in modern pharmacology and pharmaceutics. In case of nifedipine and lidocaine fixed combination such approach is quite obvious. The present review article is devoted to the analysis of clinical and non-clinical studies results on the assessment of the pharmacokinetic characteristics of these medicines. Although the oral route is the most convenient for drug administration, there are a number of circumstances where this is not possible from either a clinical or pharmaceutical perspective. In these cases, the rectal route may represent a practical alternative and can be used to administer drugs for both local and systemic actions. Research data of last decades suggested that nifedipine, a calcium channel blocker, could be effective in reducing anal resting pressure and in healing chronic anal fissure and acute thrombosed hemorrhoids. Another component of fixed combination lidocaine is a local anesthetic usually used to relieve pain of anal fissures and symptomatic hemorrhoids. In combinations lidocaine and nifedipine have complementary actions. Analysis of all available studies (during last 2 decades) which were aimed to investigate pharmacokinetic characteristics of a nifedipine and lidocaine fixed combination in the form of rectal cream showed that following topical application, the active ingredients nifedipine and lidocaine are absorbed into the bloodstream in only small quantities that have no major implications for the safety of the product, and systemic absorption, if any, was incomparably lower than absorption following per os administration of the two active ingredients.

A novel CT contrast agent for intestinal-targeted imaging through rectal administration

In this study, a novel CT contrast agent used by rectal administration is developed for targeting intestinal imaging. Iopamidol, an iodinated contrast agent, is loaded in chitosan (CS) nanospheres modified by Anti-5-HT3R (AH) antibody. The obtained AH-CS-I nanospheres (AH-CS-I Ns) would combine to 5-HT3 receptors highly expressed on the gastrointestinal mucosal, enhancing the intestinal-targeting ability of the contrast agent. The AH-CS-I Ns were administered by the rectal route for intestinal CT imaging, and FITC-labeled AH-CS-I Ns were prepared for investigating the in vivo distribution of the contrast agent. As a result, obvious contrast enhancement could still be observed at 6 h post administration because of the poorly absorption of enteral AH-CS-I Ns. Unlike the intravascularly administered agents, AH-CS-I Ns would not accumulate in the kidney and induce adverse reactions. Therefore, this technology has potential applications in the examination of intestinal diseases and could reduce the side effect of commercial iopamidol.

Effectiveness of a Single Dose of Oral Vs Rectal Paracetamol in Reducing Fever in Children Aged Between 2 to 6 years – A Randomized Controlled Trial

Background: Rectal route of paracetamol is preferred to the commonly used oral route in some instances. Yet there is no previous documented study comparing the two routes in the local setting.Methods: Single-centre, balanced randomized [1:1], two arms, parallel-group clinical trial was conducted in single Paediatric ward at the Gampaha District General Hospital, Sri Lanka. Children aged between 2-6 years with documented axillary temperature > 100° F were enrolled. Children were randomly divided into two arms with 135 participants in each arm. The first arm received single doses of 15 mg/kg oral paracetamol and second group received single doses of 30 mg/kg rectal paracetamol. A data extraction sheet was to record temperature at baseline and at 15 minutes, 30 minutes, 1 hour, 1 and1/2 hours, 2 hours, 2 and ½ hours and 3 hours after administration of the drug. The rate of temperature (time taken fever reduction by at least 1 F) reduction was calculated in 270 sample. In addition, the potential adverse events of the both groups were recorded. Results: In the oral group, mean temperature reductions at 15 minutes, 30 minutes, 1 hour, 1 and1/2 hours, 2 hours, 2 and ½ hours and 3 hours after administration of the drug were 0.11, 0.44, 1.06, 1.68, 2.10, 3.18 and 2.75 0F respectively. The respective temperature reductions in rectal group were 0.26, 0.67, 1.31, 3.52, 2.81, 3.33 and 4.45 0F. When compared the means of both groups there was statistically significant difference between two groups in all the time periods (P<0.05) except at 1 hour after administration of paracetamol (P = 0.06). There was no statistical significant difference in side effects when comparing two arms as well. Conclusion: A single dose of 30 mg/kg rectal paracetamol is more effective than single dose of 15 mg/kg oral paracetamol in reducing fever. There is no difference in relation to the safety of the two routes.Trial registration: SLCTR, SLCTR/2017/025. Registered 17 August 2017-Retrospectively registered,

MANAGEMENT OF ASRIGDARA WITH KUTAJASHTAKA AVALEHA AND YASHTIMADHU GHRITA MATRA BASTI - AN OPEN LABEL, DOUBLE ARM, RANDOMIZED CLINICAL TRIAL

Introduction: The word Asrigdara explains about prolonged, cyclic or acyclic excessive menstrual bleed-ing in Ayurveda. 9-14% of women in their reproductive age lose 80 ml of blood in each cycle. It is the most common cause of Anemia. Traditionally, Heavy Uterine Bleeding is managed with medical therapy and surgical intervention with associated side effects. But due to limitation of medical therapy as well as surgical interventions, it becomes the necessity of time to find out a permanent, easy, effective and less side effect producing care which can be easily administered and accepted by the patient. Objective: To evaluate the clinical efficacy of Kutajashtaka Avaleha orally and combination of Kutajashtaka Avaleha and Yashtimadhu Ghrita matra basti in combating the signs and symptoms of Asrigdara. Materials and Methods: 56 patients were selected from the Stri Roga and Prasuti Tantra OPD, All India Institute of Ayur-veda, New Delhi and randomly divided into 2 groups. Group A was administered with Kutajashtaka Ava-leha orally regularly for the period of 3 months with the doses of 5gm BD after meal with water, while in Group B, Combination of Yashtimadhu Ghrita Matra Basti (60 ml for 7 days in 3 consecutive cycles after meal through rectal route after 7th day of menses) for 3 months and Kutajashtaka Avaleha was given and the follow up period of 1 month without medication was same for both the groups. Results: Kutajashtaka Avaleha orally alone and Combination of Yashtimadhu Ghrita Matra Basti & Kutajashtaka Avaleha oral both gave statistically highly Significant results (P<0.001) but with better results when the treatment was combined and Markedly Improved (51-75% relief) the signs and symptoms. Conclusion: Combination of Yashtimadhu Ghrita Matra Basti & Kutajashtaka Avaleha oral gave more statistically significant results than Kutajashtaka Avaleha orally alone. No adverse effects were reported during the entire trial period.

Comparison of Coxiella burnetii Excretion between Sheep and Goats Naturally Infected with One Cattle-Associated Genotype

The main reservoir of Coxiella (C.) burnetii are ruminants. They shed the pathogen through birth products, vaginal mucus, faeces and milk. A direct comparison of C. burnetii excretions between naturally infected sheep and goats was performed on the same farm to investigate species-specific differences. The animals were vaccinated with an inactivated C. burnetii phase I vaccine at the beginning of the study period for public health reasons. Vaginal and rectal swabs along with milk specimens were taken monthly during the lambing period and once again at the next lambing season. To estimate the environmental contamination of the animals’ housings, nasal swabs from every animal were taken simultaneously. Moreover, dust samples from the windowsills and straw beddings were collected. All samples were examined by qPCR targeting the IS1111 gene and the MLVA/VNTR typing method was performed. Whole genome sequencing was applied to determine the number of IS1111 copies followed by a calculation of C. burnetii genome equivalents of each sample. The cattle-associated genotype C7 was detected containing 29 IS1111 copies. Overall, goats seem to shed more C. burnetii through vaginal mucus and in particular shed more and for longer via the rectal route than sheep. This is supported by the larger quantities of C. burnetii DNA detected in caprine nasal swabs and environmental samples compared to the ovine ones. Transmission of C. burnetii from cattle to small ruminants must also be considered.

Effectiveness of combined use of rectal misoprostol and oxytocin for prevention of postpartum hemorrhage after cesarean section

Post-Partum Hemorrhage (PPH) is defined as the loss of blood which is greater than 500ml after vaginal delivery or greater than 1000 ml after a cesarean section delivery. About 28% of the total maternal deaths were due to PPH particularly in developing countries. Oxytocin has been considered as the ‘gold standard’ drug in the treatment and prevention of PPH. Prophylactic use of prostaglandin analogue i.e., misoprostol in addition to oxytocin during cesarean section is expected to reduce the incidence of PPH. This study aims at comparing the efficacy of combined use of rectal misoprostol and oxytocin infusion with oxytocin in the prevention of PPH. A comparative observational study was conducted on 200 subjects which were divided into two equal groups by Simple Random Selection. One group was treated with Inj. Oxytocin 20U I.V infusion alone while the other group was treated with Tab. Misoprostol 600mcg, rectal route and Inj. Oxytocin 20U I.V infusion. Majority of the subjects were observed under the age group of 21-25years, under primigravidae. A significant decrease in the volume of mean blood loss (740.00 ± 164.00 ml: p = 0.045) and the mean drop of hemoglobin level(Hb) (0.88±0.74gm/dl; p = 0.0001) were observed in group treated with Tab. Misoprostol 600mcg and Inj. Oxytocin and was found to be statistically significant. Preoperative administration of misoprostol per rectal route and oxytocin infusion after the cesarean section have shown, a better control of bleeding and maintenance of hemoglobin level when compared to oxytocin infusion alone. Thus, instead of oxytocin monotherapy combined use of misoprostol and oxytocin would be more effective in prevention of PPH.