Used Route Of Administration Research Articles

Pharmacokinetics of intranasal and intramuscular flunixin in healthy grower pigs.

Flunixin meglumine is a nonsteroidal anti-inflammatory drug approved to manage pyrexia associated with swine respiratory disease. In the United States, no analgesic drugs are approved for use in swine by the FDA, although they are needed to manage painful conditions. This study evaluated the pharmacokinetics and relative bioavailability of intranasal versus intramuscular flunixin in grower pigs. Six pigs received 2.2 mg/kg flunixin either intranasally via atomizer or intramuscularly before receiving flunixin via the opposite route following a 5-day washout period. Plasma samples were collected over 60 h and analysed using ultra-performance liquid chromatography and tandem mass spectrometry to detect flunixin plasma concentrations. A non-compartmental pharmacokinetic analysis was performed. The median Cmax was 4.0 μg/mL and 2.7 μg/mL for intramuscular and intranasal administration, respectively, while the median AUCinf was 6.9 h μg/mL for intramuscular administration and 4.9 h μg/mL for intranasal administration. For both routes, the median Tmax was 0.2 h, and flunixin was detectable in some samples up to 60 h post-administration. Intranasal delivery had a relative bioavailability of 88.5%. These results suggest that intranasal flunixin has similar, although variable, pharmacokinetic parameters to the intramuscular route, making it a viable route of administration for use in grower swine.

A Glance on Mucoadhesive System - Still more to Understand

Most popular and useful route of administration is oral one, among that mucoadhesive system is also preferable. This system is interact with mucus layer containing epithelial cell and mucin molecules which improves the contact time of dosage form, leading to improvement in both local and systemic effects. There are various routes of mucoadhesive drug delivery system, oral route is the most oldest and preferred by patient being convenient to use. However peroral route has some disadvantages such as hepatic first pass metabolism and enzymatic degradation in GIT which is a hindrance to the absorption of most proteins and peptides groups of drugs. The mucosa of the oral cavity contains an intimidating barrier to drug penetration, and one method of optimizing drug delivery is by the use of adhesive dosage forms and the mucosa is connected with various blood supplies by which it is permeable. This route has quick action, and good patient compliance with pediatric and old age patients. The buccal cavity is very easier for a bioadhesion system because of a smooth and relatively immobile surface and accessibility. Mucoadhesion can be achieved by using various mucoadhesive polymers. There are various types of mucoadhesive polymers which improves bioadhesion. Also various theories are referred to clear the concept of mucoadhesion, such as diffusion, facture, electronic and adsorption theories. This article contains definition, mechanism, advantage, and disadvantage. In this article we are going to overlook basic knowledge about mucoadhesion and its formulations.

Tocopheryl phosphate mixture (TPM) as a novel lipid-based transdermal drug delivery carrier: formulation and evaluation.

Transdermal drug delivery is a useful route of administration that avoids first-pass metabolism and more invasive delivery options. However, many drugs require enhancers to enable sufficient drug absorption to reach therapeutic effect. Alpha-tocopheryl phosphate (TP) and di-alpha-tocopheryl phosphate (T2P) are two phosphorylated forms of vitamin E which form tocopheryl phosphate mixture (TPM) when combined, and have been proposed to enhance the dermal and transdermal delivery of actives of interest. Here, we report the physicochemical characteristics and morphological properties of TPM formulations, including particle size, deformability and morphology, and its ability to facilitate the transport of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, and across, the skin. Results demonstrate that TPM self-assembles to form vesicular structures in hydroethanolic solutions ranging in mean size from 101 to 162nM depending on the amount of TPM and ethanol present in the formulation. The ratio of TP to T2P in TPM formulations altered vesicle size and elasticity, with vesicles high in TP found to be more deformable than those rich in T2P. TPM produced a significant (p<0.05) 2.4-3.4-fold increase in the absorption of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, or through, the skin. The TPM delivery platform was able to deliver a diverse range of actives with differing size and solubility profiles and therefore has significant potential to expand the number and types of drugs available for topical application and transdermal delivery.

Buccal drug delivery: what's new and what does the future hold?

The buccal mucosa is the stratified squamous epithelial tissue inside lining of the cheeks. It is a favorable site of drug absorption since the tissue is non-keratinized, relatively immobile and strongly supplied with blood by a dense capillary-vessel network; moreover, it is highly tolerant to allergens, resistant to potentially harmful agents and has a relatively low enzymatic activity. The tissue consents quick onset of effect, offers an easily accessible and generally well-accepted site for drug delivery, is a useful route of administration in patients in an unconscious state (e.g., when swallowing is impaired), and is suitable for retentive dosage forms of administration. Buccal mucosa allows drug delivery for both locoregional and systemic treatments. Locoregional delivery has a number of applications, including treatment of local conditions, such as mucositis, bacterial and fungal infections, aphthous stomatitis, vesiculobullous diseases, and potentially malignant disorders and oral cancer. On the other hand, the tissue is appropriate for delivering systemically acting drugs. The actives directly enter general circulation through capillary vessels, bypassing the first-pass metabolism in the intestine and liver, avoiding presystemic drug elimination or chemical/enzymatic degradation within the gastrointestinal tract thus leading to high bioavailability. “If low concentrations of drug are required to gain access to the blood, transbuccal drug delivery may be very satisfactory for safe and well-accepted future clinical applications” [1–3]. Controlled delivery of drugs through the buccal mucosa should be considered like a slow intravenous infusion. These characteristics contribute to optimal pharmacokinetic behavior of drugs after administration of smaller doses than in conventional oral formulations [4]. Nevertheless, similar to other mucosal membranes, the buccal mucosa has some disadvantages, including short residence time and small absorption area. The major limitation to buccal drug delivery is the barrier property of the tissue which has inadequate permeability for certain molecules, resulting in low drug bioavailability. Drug absorption is very satisfactory only for those actives that possess adequate physicochemical properties and the ability to permeate across the tissue. Accordingly, the formulative approach alone could be not sufficient for an effective control of drug delivery through the mucosa, and limited rate of absorption should be adjusted by simultaneous chemical and physical enhancement, including supersaturation and eutectic formation [4,5]. Buccal dosage forms reside in a tastesensing organ, and organoleptic aspects of formulation could become crucial limiting factors for drug application. Suitable palatal properties are often required to get optimal acceptability of dosage form or for masking less desirable properties of the active component [6]. Despite offering the possibility of improved systemic drug delivery, buccal administration has been utilized for relatively few pharmaceutical products so far. Conventional dosage forms, such as solutions, are commercially available for Buccal drug delivery: what’s new and what does the future hold?

Effects of Subconjunctival Injection of Anti-Vascular Endothelial Growth Factor Antibody on Oxygen-Induced Ischemic Retinopathy in a Neonatal Rat Model

The present study investigated the effects of subconjunctival injections of an anti-rat vascular endothelial growth factor (anti-VEGF) antibody on oxygen-induced retinopathy (OIR) in a neonatal rat model. OIR was induced by daily cycles of 80% oxygen (20.5h), room air (0.5h), and a progressive return to 80% oxygen (3h) for 12 days [until postnatal day (P) 12]. On P12, rats received subconjunctival injections in their right eye of 0.1 or 1.0μg anti-VEGF antibody (or 1.0μg goat IgG as a control). No injections were made into the left eye. On P18, rats were killed and their retinas were removed and flat-mounted before being stained with adenosine diphosphatase. Retinal neovascularization (NV) was scored and the extent of avascular areas, as a percentage of total retinal area (%AVA), was determined using image analysis. Although there was a tendency for lower mean NV scores in eyes injected with 0.1 and 1.0μg anti-VEGF compared with control (4.3±1.1, 2.3±1.0, and 6.7±1.3, respectively; n=10–13), the difference failed to reach statistical significance. Similarly, although there was a tendency for mean %AVA to be lower in the injected eyes for both the 0.1 and 1.0μg anti-VEGF groups compared with control (15±3%, 13±3%, and 25±4%, respectively; n=10–13), the differences were not significant. Similar tendencies were observed in the contralateral eyes. Although further studies using larger numbers of rats are needed to obtain statistically significant results, the results of the present study suggest that the subconjunctival injection of anti-VEGF antibody may prove to be a useful route of administration in conjunction with intravitreal injections, which are the generally used method at present. However, careful attention should be paid to the possibility of systemic side effects.

An Alternative Approach to Tuberculosis Management with Intravenous Streptomycin

Streptomycin is currently utilized to treat advanced tuberculosis in Korea. However, the usefulness of intravascular streptomycin is not fully understood. In this study, streptomycin was administered intravenously in 30 patients. Intravenous administration of streptomycin may be a useful route of administration without undesirable toxicities.

Rational Use of Sublingual Opioids in Palliative Medicine

The sublingual administration of opioid analgesics has been a mainstay in the pain management of homebound dying hospice patients who are no longer able to swallow. It is also a potentially useful route of administration in other situations in which the oral route is not available and other routes are impractical or inappropriate. Potential advantages of the sublingual route include rapid analgesic onset and avoidance of hepatic first-pass metabolism. Pharmacokinetic and pharmacodynamic studies have yielded widely disparate data on sublingual morphine. Other opioids have been less studied. Available data suggests limited sublingual availability of hydrophilic opioids (e.g., morphine, oxycodone, and hydromorphone) and superior absorption of the lipophilic opioids (e.g., methadone and the fentanils). Buprenorphine, a potent, lipophilic, partial mu-opioid receptor agonist, appears promising but awaits further study.

Pharmacokinetics of glycine–proline–glutamate, the N-terminal tripeptide of insulin-like growth factor-1, in rats

Glycine–proline–glutamate (GPE) is the N-terminal tripeptide of insulin-like growth factor-1 and has been shown to be neuroprotective following ischemia-induced brain injury. The pharmacokinetics of GPE were studied in adult rats since GPE is a candidate for use in neuroprotection therapies. To measure plasma concentrations of GPE a novel radioimmunoassay was developed whereby GPE was initially derivatized with Bolton and Hunter reagent before use in a standard homologous assay against the Bolton and Hunter iodinated form. The derivatized GPE radioimmunoassay showed a 83% recovery of unlabeled GPE and complete parallel displacement with rat plasma. The simplicity and speed of the assay described here indicate an exciting new use for a previously described technology. The pharmacokinetic studies were conducted in adult rats using a single bolus intravenous injection of GPE at 30 or 100 mg/kg and showed that GPE was rapidly cleared from the circulation. In addition, evidence of the route of the metabolic degradation of GPE is presented. The findings presented here are the first description of the pharmacokinetics of GPE and suggest that, because of its very short half-life in plasma, continuous intravenous infusion of GPE may be the preferred route of administration for use in future neuroprotection therapies.

Pharmacokinetics of intrathecal transferrin-ricin A chain immunotoxin

We have studied the pharmacokinetics of an anti transferrin receptor immunotoxin following intrathecal (i.t.) and intravenous (i.v.) bolus inoculation in healthy rats. After i.t. inoculation of 4.9 μg transferrin-ricin A-chain (Tfn-RTA) we have measured the immunotoxin concentration in the cerebrospinal fluid (CSF), in the brain tissue and in the peripheral blood. After i.v. administration of 4.9 μg Tfn-RTA the concentration of Tfn-RTA immunotoxin was evaluated in the peripheral blood. We found that the clearance of Tfn-RTA from the CSF is rapid (9.1 μLmin −1), the immunotoxin then diffuses into the brain tissue and in the peripheral blood where it reaches concentrations below the MTC 50 (Minimum Toxin Concentration 50%). The rate of immunotoxin elimination from the peripheral blood following either i.v. or i.t. administration are similar (k el = 0.0021 min −1 vs. 0.0025 min −1). Thus, in the healthy rat the immunotoxin does not accumulate following i.t. inoculation, reaching non toxic concentrations in the brain tissue and in the peripheral blood, whereas in the CSF as well as at the interface CSF/brain tissue the immunotoxin may reach potentially therapeutic concentrations. In conclusion we believe that the i.t. inoculation of an immunotoxin could be considered a potentially useful route of administration in the treatment of leptomeningeal carcinomatosis.

Intravenous Streptomycin: A Useful Route of Administration

Streptomycin is an aminoglycoside antibiotic that is indicated for the treatment of tuberculous and nontuberculous infections. Intramuscular injection is the recommended route of administration. There are few reports on intravenous administration of streptomycin. We describe the use of intravenous streptomycin to treat endocarditis due to a strain of Enterococcus faecalis with high-level resistance to gentamicin. Physicians should consider the intravenous route as an alternate method of administering streptomycin.

Pharmacokinetics of intraperitoneal teicoplanin in patients with chronic renal failure on continuous ambulatory peritoneal dialysis.

The pharmacokinetic profile of teicoplanin, a new glycopeptide antibiotic active against Gram-positive aerobic and anaerobic bacteria, is described in five patients with end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD). A single 3 mg kg-1 dose was given intraperitoneally in the dialysate during a 6 h dwell time. The drug appeared in the plasma within 15 min at 1.00-0.28 mg l-1 (mean +/- s.d. = 0.70 +/- 0.45) in all five subjects, and peak serum concentrations ranged from 5.53 to 2.80 mg l-1 (4.84 +/- 1.43) at 6 h. Approximately 70% (71 +/- 12) of teicoplanin was absorbed from the peritoneal dialysis fluid during a single 6 h dwell time. The rate constant for peritoneal transfer (lambda d) averaged 0.318 h-1 and the half-life (t1/2 lambda d) was 2.18 h. Further values were serum elimination half-life 114-173 h; total body clearance 263-532 ml h-1; steady-state volume of distribution 68-93 l. This drug profile closely agrees with data reported after intravenous injection in patients on CAPD and suggests that teicoplanin has bidirectional exchange characteristics through the peritoneal membrane, although transfer from the systemic circulation to peritoneal fluid is consistently low. Instillation of teicoplanin in CAPD fluid may be a useful route of administration for treatment of peritonitis and exit site infections in CAPD patients.