Administration Of Oral Solution Research Articles

Pain treatment individualization in patients with advanced cancer using immediate release morphine

Adequate pain relief through individual tailoring of the basic analgesic in suited dose and drug formulation, as well as the use of adjuvant and supportive therapy, relieves the suffering of patients with advanced cancer in most cases. Noninvasive opioids in immediate and modified release formulations play a key role in treating severe chronic pain syndrome. We present a series of case studies to illustrate morphine tablet and oral solution administration as part of an individual pain therapy regimen, such as opioid dose titration, treatment of breakthrough pain, and around-the-clock pain control.

Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice.

Intranasal delivery is a non-invasive mode of administration, gaining popularity due to its potential for targeted delivery to the brain. The anatomic connection of the nasal cavity with the central nervous system (CNS) is based on two nerves: olfactory and trigeminal. Moreover, the high vasculature of the respiratory area enables systemic absorption avoiding possible hepatic metabolism. Due to these physiological peculiarities of the nasal cavity, compartmental modeling for nasal formulation is considered a demanding process. For this purpose, intravenous models have been proposed, based on the fast absorption from the olfactory nerve. However, most of the sophisticated approaches are required to describe the different absorption events occurring in the nasal cavity. Donepezil was recently formulated in the form of nasal film ensuring drug delivery in both bloodstream and the brain. In this work, a three-compartment model was first developed to describe donepezil oral brain and blood pharmacokinetics. Subsequently, using parameters estimated by this model, an intranasal model was developed dividing the administered dose into three fractions, corresponding to absorption directly to the bloodstream and brain, as well as indirectly to the brain expressed through transit compartments. Hence, the models of this study aim to describe the drug flow on both occasions and quantify the direct nose-to-brain and systemic distribution.

Pharmacokinetics of single and repeated oral doses of pregabalin oral solution formulation in cats

The study was designed to determine the pharmacokinetic profile and bioavailability of a novel pregabalin 50 mg/ml oral solution formulation (Bonqat®, Orion Corporation Orion Pharma) in 6 healthy laboratory cats. The cats received pregabalin as single oral doses of 2.5, 5, and 7.5 mg/kg, dose 5 mg/kg on two consecutive days, and a single intravenous dose of 2.5 mg/kg. The washout period between each administration was four weeks. The cats were monitored for clinical signs and level of sedation, and blood samples were taken before pregabalin dosing and at pre‐defined time points up to 168 h after dosing. Plasma concentrations of pregabalin were determined using a validated liquid chromatography–tandem mass spectrometry method. The mean maximum plasma concentration of 10.1 μg/ml was reached between 0.5 and 1 h after oral administration of the clinical dose 5 mg/kg. The mean half‐life after oral administration of dose 5 mg/kg was 14.7 h and the mean systemic bioavailability was 94%. Pregabalin showed linear pharmacokinetics from 2.5 to 7.5 mg/kg. Exposures after a single dose and re‐dosing of 5 mg/kg at 24 h were comparable. Pregabalin was well tolerated with mild sedation and mildly uncoordinated movements observed in few cats at dose 7.5 mg/kg. As a conclusion, study results show rapid absorption, linear pharmacokinetics, and high oral bioavailability of pregabalin without safety concerns after administration of oral solution in cats.

Indigenous management of Dystocia in ruminant livestock of northern guinea savanna of Nigeria

This study, conducted in Bauchi and Zaria areas of the northern guinea savanna zone of Nigeria involved livestock that encountered problems during parturition Ninety eight Hausa-Fulani livestock holdings involving cattle, sheep and goats were investigated. The study focused on causes of and remedies for dystocia. The study showed that farmers have traditional means of handling difficult birth in ruminants. The identifiable causes of dystocia included age and size of dam, abnormal foetal presentation, poor health, multiple foetuses and weight and sex of the young. The management of this problem included the use of hand to correct foetal position, lubrication of the vulvo-vagina passage with mashed okra fruit for easy passage, and oral administration of solutions from native herbs, snake scales, potash and ashes.

Rupatadine oral solution for 2-5-year-old children with allergic rhinitis: a safety, open-label, prospective study.

BackgroundThere are few clinical trials that assess the efficacy of antihistamines in very young children. Rupatadine is a second-generation antihistamine indicated for the treatment of allergic rhinitis (AR) and urticaria. In this study, AR symptoms were evaluated before and after daily 1 mg/mL rupatadine oral solution administration in 2–5-year-old children.MethodsA multicenter open-label study was carried out in 2–5-year-old children with AR. Safety assessments were collected during the study including spontaneous adverse events, vital signs, and electrocardiogram (QTc interval). Additionally, evaluations of Total Five Symptoms Score (T5SS, including: nasal congestion; sneezing; rhinorrhoea; itchy nose, mouth, throat, and/or ears; and itchy, watery, and red eyes) were analyzed. Symptoms were evaluated by parents/legal guardian before and after 4 weeks of rupatadine administration, dosed according to body weight.ResultsA total of 44 children received the study treatment. Only 15 adverse events were reported. All of them were of mild intensity and considered not related to the study treatment. No patient exceeded the standard parameter of >450 ms in the last visit, for the QTc interval on their electrocardiograms. From a maximum score value of 15, T5SS values at Day 14 (6.35) and Day 28 (5.42) were both statistically significant different (p<0.001) from the baseline T5SS value (mean 8.65), with a reduction of 26.6% and 37.4%, respectively. All individual symptoms, including nasal congestion, showed also a decrease from baseline at both 14 and 28 days.ConclusionRupatadine 1 mg/mL oral solution was found to be safe in 2–5-year-old children, correlating with an improvement of AR symptoms, overall and each individually, after a daily dose administration. With this study, we enlarge the available information in this very young pediatric patients’ group, in which there is a general lack of clinical evidence.

Administration of Direct Oral Anticoagulants Through Enteral Feeding Tubes

Objective: To review literature regarding direct oral anticoagulants (DOACs) and determine their viability of administration in solution or via enteral tubes. Data Sources: MEDLINE literature searches identified articles published 2007-present using MeSH terms: factor Xa inhibitors, antithrombins, biological availability, and enteral nutrition. Package inserts were included. Manufacturers were asked to provide literature. Study Selection and Data Extraction: We included studies emphasizing bioavailability or enteral administration. Data Synthesis: Dabigatran and edoxaban package inserts recommend against altering the dosage form, and against enteral administration. One rivaroxaban study was identified. Given with food, enteral administration was comparable to the oral tablet. The mean AUC (0.889, 90% CI 86.12-91.84%) was within the equivalency margins; however Cmax (0.820, 90% CI 78.84-85.86%) was slightly below the 80% threshold. One apixaban study was identified. They showed bioequivalence between oral and enteral administration in different vehicles, but decreased bioavailability when crushed tablets were given along with nutritional support. AUC and Cmax were 32% and 19% lower, respectively, when apixaban solution was given via nasogastric (NG) tube with nutritional supplement versus oral administration of solution. Conclusions: Dabigatran capsules should not be altered, due to large variations in drug exposure. Rivaroxaban can be given as oral solution or via NG tube. Larger doses must be given with nutritional supplementation and enteral tubes must not be distal to the stomach. Apixaban can be given as oral solution or via nasogastric or gastric tube on an empty stomach. Food impairs bioavailability of the crushed tablets. There are insufficient data to recommend enteral administration of edoxaban and the package insert recommends against altering tablets.

Tapioca starch blended alginate mucoadhesive-floating beads for intragastric delivery of Metoprolol Tartrate

The objective of the study was to develop tapioca starch blended alginate mucoadhesive-floating beads for the intragastric delivery of Metoprolol Tartrate (MT). The beads were prepared by ionotropic gelation method using calcium chloride as crosslinker and gas forming calcium carbonate (CaCO3) as floating inducer. The alginate gel beads having 51–58% entrapped MT showed 90% release within 45min in gastric medium (pH 1.2). Tapioca starch blending markedly improved the entrapment efficiency (88%) and sustained the release for 3–4h. A 12% w/w HPMC coating on these beads extended the release upto 9–11h. In vitro wash off and buoyancy test in gastric media revealed that the beads containing CaCO3 has gastric residence of more than 12h. In vitro optimized multi-unit formulation consisting of immediate and sustained release mucoadhesive-floating beads (40:60) showed good initial release of 42% MT within 1h followed by a sustained release of over 90% for 11h. Pharmacokinetic study performed in rabbit model showed that the relative oral bioavailability of MT after administration of oral solution, sustain release and optimized formulation was 51%, 67% and 87%, respectively. Optimized formulation showed a higher percent inhibition of isoprenaline induced heart rate in rabbits for almost 12h.

Relative Bioavailability of Apixaban Solution or Crushed Tablet Formulations Administered by Mouth or Nasogastric Tube in Healthy Subjects

PurposeCrushed tablet and solution formulations of apixaban administered orally or via a nasogastric tube (NGT) may be useful in patients unable to swallow solid dose formulations. It is important to understand whether new formulations and/or methods of administration impact apixaban bioavailability and pharmacokinetic properties. These studies evaluated the relative bioavailability (Frel) of apixaban solution administered orally; oral solution administered via NGT flushed with either 5% dextrose in water (D5W) or with infant formula; oral solution via NGT with a nutritional supplement; and crushed tablet suspended in D5W and administered via NGT. MethodsThree open-label, randomized, crossover studies were conducted in healthy adults (study 1: apixaban 10-mg tablet [reference] versus oral solution, both administered PO; study 2: apixaban 5-mg oral solution PO [reference] versus oral solution via NGT flushed with either D5W or infant formula; study 3: apixaban 5-mg oral solution PO [reference] versus apixaban 5-mg oral solution via NGT with a nutritional supplement and versus crushed tablet suspended in D5W and administered via NGT). Point estimates and 90% CIs of the geometric mean ratios (GMRs; test/reference) were generated for Cmax and AUC. Adverse events were recorded throughout each study. FindingsFrel of the oral solution was 105% versus tablet, and Frel for oral solution via NGT with D5W flush, infant formula flush, nutritional supplement, and crushed tablet via NGT versus oral solution administration were 96.7%, 92.2%, 81.3%, and 95.1%, respectively. The 90% CIs of the GMRs of all AUCs met the bioequivalence criterion except that of the nutritional supplement (0.766–0.863). The corresponding GMRs for Cmax were 0.977, 0.953, 0.805, 0.682, and 0.884. For the solution via NGT flushed with D5W and for the crushed tablet, the 90% CIs of the Cmax GMRs met the bioequivalence criterion. Apixaban was well tolerated in all 3 studies; most adverse events were mild. ImplicationsComparable Frel was observed for oral apixaban solution, tablet, NGT administration of solution flushed with D5W and infant formula, and NGT administration of crushed tablet suspension. Exposure was less when oral solution was administered via NGT with nutritional supplement. These results support several alternative methods of administering apixaban that may be useful in certain clinical situations. ClinicalTrials.gov identifiers: NCT02034565, NCT02034578, and NCT02034591.

Relative bioavailability of a prototype oral solution of the Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors

Alisertib (MLN8237) is an investigational, oral, small-molecule, selective inhibitor of Aurora A kinase. Phase I/II studies of powder-in-capsule (PIC) and enteric-coated tablet formulations of alisertib have determined the recommended phase II dose and have demonstrated anti-tumor activity. This phase I relative bioavailability study characterized the pharmacokinetics of a prototype oral solution (OS) of alisertib (developed for patients unable to swallow solid dosage forms) in reference to the PIC formulation in adult cancer patients. A safety evaluation was undertaken first following a 3+3 design (OS starting dose, 15 mg). The relative bioavailability of alisertib OS vs. PIC was then evaluated following single dose administration of alisertib OS 25 mg and PIC 50 mg, using a 2-way crossover study design. The relative bioavailability (geometric mean dose-normalized AUCinf ratio) of alisertib OS vs. PIC formulation was 1.26 (90% confidence interval (CI): 1.09-1.47 (OS, n=17; PIC, n=18 evaluable patients)). These results support a distinguishable difference in bioavailability of alisertib between the two formulations (lower bound of 90% CI>1), with an estimated 26% higher total systemic exposure with alisertib OS vs. PIC. Alisertib absorption from OS was faster than from PIC, with a shorter median tmax (OS, 1 hour; PIC, 2 hours) and a geometric mean dose-normalized Cmax ratio (OS vs. PIC) of 1.90 (90% CI: 1.52 - 2.37). These findings inform the starting dose of alisertib OS to support further clinical evaluation of alisertib in patients unable to swallow solid dosage forms.

Evaluation of D-ribose pharmacokinetics, dose proportionality, food effect, and pharmacodynamics after oral solution administration in healthy male and female subjects

This was a double blind, randomized, crossover study of three periods evaluating pharmacokinetics and pharmacodynamics in 12 healthy, adult subjects after administration of D-ribose powder for oral solution, 2.5, 5.0, and 10.0 g, under fasting conditions followed by an open label, randomized, fourth period assessing the effect of food on the pharmacokinetics of D- ribose (10.0 g) under fed conditions with either a high fat (HF, N = 6) or high carbohydrate (HC, N = 6) meal. D-ribose was absorbed rapidly with mean Tmax ranging between 18 and 30 minutes. Cmax and AUC increased more than proportionally with dose indicating increased absorption and saturation of metabolism. When D-ribose was administered with meals, Tmax was unchanged; however, Cmax and AUC decreased by 42.6% and 40.8%, respectively with HF and 69.1% and 64.9%, respectively with HC. The amount of D-ribose in urine ranged from 4.15% to 7.20% of the administered dose. Dose-related decreases in serum glucose up to 26.3 mg/dL (30.3% of baseline) occurred in the first 60 minutes post dose and insulin response attained a dose-related peak 15 minutes post dose. D-ribose was generally safe and well tolerated in the dose range studied.

IMPROVEMENT THE RELEASE AND AVAIALBILITY OF CELECOXIB CO-ADSORBATE FROM FLOATING CAPSULES

Celecoxib is a selective COX-2 inhibitor non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. Celecoxib is practically inslouble in GIT pH. Consequently, it suffers from low and variable bioavailability following oral administration of solutions (64-88%) and capsules (20-40%) In the present study, gastroretentive controlled release single-unit floating capsules of Celecoxib were designed and evaluated. Various grades of low and high viscosity polymers of HPMC 4000 and 15.000 cps and NaCMC were used for formulation of Celecoxib capsules. For the purpose of enhancing the poor dissolution rate of Celecoxib, co-adsorption with Tween 80 onto surface of Florite® was investigated in this study. Thus, controlled release limited by drug solubility was percluded and delivery of active material was controlled by the formulation. In the present study conventional capsules containing Celecoxib using HPMC and NaCMC were developed and evaluated. Floating capsules containing Celecoxib, co-adsorption with Tween 80 onto surface of Florite and Aerosil 200 in different ratios were also formulated and investigated for the release of the drug from these capsules. The results obtained of this study showed that Celecoxib capsules containing HPMC 15000cps as a swelling matrix has a good floating behaviour and retarding effect on the drug release. Also, different concentrations of sodium bicarbonate confirmed and maintained the floating properties of the prepared formulations without affecting the drug release. From DSC and X-ray diffraction studies it was found that crystalline Celecoxib was converted into the amorphous form in the presence of Florite® at (1:5 w/w drug: carrier ratio) in the adsorbate and co-adsorbate with Tween 80. The loaded and ground mixtures of Celecoxib with either Florite® or Aerosil 200 increased the dissolution rate of the drug. Furthermore, co-adsorbate of the drug with Florite® and Tween 80 at these ratios of (1:5:3 and 1:5:5) gave the highest percentage released of Celecoxib (reached about 100% at 30 and 45 min., respectively).

Colon-targeted celecoxib-loaded Eudragit® S100-coated poly-ϵ-caprolactone microparticles: Preparation, characterization and in vivo evaluation in rats

Context: Celecoxib suffers from low and variable bioavailability following oral administration of solutions or capsules. Recent studies proved that chemoprevention of colorectal cancer is possible with celecoxib.Objective: This work aimed to tailor colon-targeted celecoxib-loaded microparticles using time-dependant and pH-dependant coats. Estimation of drug pharmacokinetics following oral administration to fasted rats was another goal.Methods: A 23 factorial design was adopted to develop poly-ϵ-caprolactone (PCL) celecoxib-loaded microparticles (F1–F8). To minimize drug-percentages released before colon, another coat of Eudragit® S100 was applied. In vitro characterization of microparticles involved topography, determination of particle size and entrapment efficiency (EE %). Time for 50% drug release (t50%) and drug-percentages released after 2 hours (Q2h) and 4 hours (Q4h) were statistically compared. Estimation of drug pharmacokinetics following oral administration of double-coat microparticles (F10) was studied in rats.Results: PCL-single-coat microparticles were spherical, discrete with a size range of 60.66 ± 4.21–277.20 ± 6.10 μm. Direct correlations were observed between surfactant concentration and EE%, Q2h and Q4h. The PCL M.wt. and drug: PCL ratio had positive influences on EE% and negative impacts on Q2h and Q4h. When compared to the best achieved PCL-single-coat microparticles (F2), the double-coat microparticles (F10) showed satisfactory drug protection; Q2h and Q4h were significantly (P < 0.01) decreased from 31.84 ± 1.98% and 54.72 ± 2.10% to 15.92 ± 1.78% and 26.93 ± 2.76%, respectively. When compared to celecoxib powder, F10 microparticles enhanced the bioavailability and extended the duration of drug-plasma concentration in rats.Conclusion: The developed double-coat microparticles could be considered as a promising celecoxib extended-release colon-targeting system.

An improved technique for oral administration of solutions of test substances to experimental rats using Mediflon/Medicut intravenous cannula

The oral administration of solution of drugs or test substances to experimental rats is often necessary in various pharmacological, toxicological and other biomedical researches. It is scientifically sound and preferable to administer test substances to experimental animals by the same route(s) by which it is taken or meant to be taken by humans as systemic bioavailability; pharmacokinetics and toxicological parameters obtained for the substance will depend markedly on the route used to administer it. The non-ready availability of the standard oral cannula designed for varieties of animals and widespread dearth of technical skills to properly use available improvised techniques in this part of the world has made this route somewhat unpopular among biomedical scientists. In several instances it is abandoned even though initially opted for. This paper narrates and illustrates the technique of using a size 18G Mediflon/Medicut intravenous cannula as an improvised oral cannula to administer solutions of drugs and test substances to experimental rats. Techniques of handling and manipulating the rat with the goal of having the eosophagus as straight as possible and of the oral introduction of the Mediflon/Medicut cannula attached to a syringe containing the solution of test substance are narrated and then illustrated by pictures. The usual problems and difficulties encountered with the oral administration of solutions of test substances using either the syringe alone or introducing it into the feeds or drinking water of the rats were avoided. And the intended doses were accurately delivered at every instance this improvised oral cannula was used. Key words: Oral administration, Mediflon/Medicut intravenous cannula.

An improved technique for oral administration of solutions of test substances to experimental rats using Mediflon/Medicut intravenous cannula

The oral administration of solution of drugs or test substances to experimental rats is often necessary in various pharmacological, toxicological and other biomedical researches. It is scientifically sound and preferable to administer test substances to experimental animals by the same route(s) by which it is taken or meant to be taken by humans as systemic bioavailability; pharmacokinetics and toxicological parameters obtained for the substance will depend markedly on the route used to administer it. The non-ready availability of the standard oral cannula designed for varieties of animals and widespread dearth of technical skills to properly use available improvised techniques in this part of the world has made this route somewhat unpopular among biomedical scientists. In several instances it is abandoned even though initially opted for. This paper narrates and illustrates the technique of using a size 18G Mediflon/Medicut intravenous cannula as an improvised oral cannula to administer solutions of drugs and test substances to experimental rats. Techniques of handling and manipulating the rat with the goal of having the eosophagus as straight as possible and of the oral introduction of the Mediflon/Medicut cannula attached to a syringe containing the solution of test substance are narrated and then illustrated by pictures. The usual problems and difficulties encountered with the oral administration of solutions of test substances using either the syringe alone or introducing it into the feeds or drinking water of the rats were avoided. And the intended doses were accurately delivered at every instance this improvised oral cannula was used.

Enhancement of transdermal delivery of theophylline using microemulsion vehicle

A microemulsion vehicle had been studied as a possible matrix for transdermal delivery of theophylline. The existence of microemulsion regions were investigated in pseudo-ternary phase diagrams, and various microemulsion formulations were prepared using oleic acid, Cremophor RH40/Labrasol (1:2) and water. The optimal formulation of the microemulsion was evaluated in vitro using Franz diffusion cells. The droplet size of microemulsion was characterized by photo correlation spectroscopy. Pharmacokinetic study in vivo was conducted using rabbits, and the results indicated that AUC 0→∞ of transdermal administration was 1.65-fold higher than that of oral solution administration. These studies showed that microemulsion system of theophylline might be promising vehicles for the transdermal delivery of theophylline.

Atypical dose–route-dependent food effects of eplerenone in the dog: Presence of food effects following intravenous dosing and lack of food effects of following oral dosing

This study was conducted to investigate why a food effect was observed following an intravenous dose of eplerenone (EP) in the dog, but not following oral dosing. Three female dogs were implanted with a chronic portal vein access port and received radiolabeled EP doses orally (15 mg/kg in solution) and intravenously (7.5 mg/kg via cephalic and portal veins) under fasted and fed conditions. Mean AUC values for EP after infusion through the cephalic vein were 23.0 ± 2.7 and 18.2 ± 1.1h · μg/mL under fasted and fed conditions, respectively. Corresponding values after infusion through the portal vein were 20.7 ± 3.2 and 12.9 ± 1.3h · μg/mL, respectively. After oral administration, EP was absorbed 82.0 ± 6.9 and 98.0 ± 8.3% under fasted and fed conditions; corresponding mean AUC values were 32.0 ± 2.0 and 30.8 ± 3.6h · μg/mL, respectively. The AUC value for SC-70303 acid (the open lactone form of EP) was lower under fed conditions after cephalic vein infusion, but was greater under fed conditions after portal vein infusion or oral solution administration. The hepatic first-pass effect of EP was 12.6 ± 6.3% under fasted conditions and 27.1 ± 6.0% under fed conditions. Pharmacokinetic analysis of EP concentrations after portal vein infusion and oral administration showed that under fed conditions the rate constants for bile excretion and for liver metabolism and urinary excretion were increased while the rate constant for elimination and/or metabolism in the gastrointestinal tract was reduced. In conclusion, the apparent lack of food effect after oral administration was observed because enhanced clearance was compensated by increased absorption. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:607–614, 2002

長期経管栄養施行中の重症心身障害者に対する亜セレン酸ナトリウム内服液投与の有用性

Selenium is a component of glutathione peroxidase (GPx), which metabolizes oxygen radicals. Generally, selenium is obtained from such foods as grains and fish. Therefore, for patients with severe motor and intellectual disabilities (SMID) who cannot orally consume meals, a selenium deficiency remains a problem. To overcome this problem, selenium oral solution was administered to SMID patients under long-term total parenteral nutrition, and the usefulness of selenium oral solution was evaluated using the serum selenium concentration and GPx activity as indices.Before selenium oral solution administration, the serum selenium concentration of SMID patients was 3.0 ± 0.7, μg/dL, which is an extremely the low value compared with 11.2 ± 1.2, μg/dL which is the normal value for a healthy adult. Moreover, the GPx activity of 48.5 ± 12.3 n mol/min/mL was also extremely low in comparison to a healthy adult' s value of 112.6 ± 5.6 n mol/min/mL. When a selenium oral solution (6, μg/kg) was administered to SMID patients for two weeks once per day, the serum selenium concentration and the GPx activity increased, and there was no difference from a normal healthy adult' s value. Although the selenium oral solution thereafter decreased to 1.5μg/kg once per day, the serum selenium concentration and the GPx activity were mostly maintained in the normal region. Moreover, a significant positive correlation was observed between the serum selenium concentration and the GPx activity. (p< 0.001)These results suggested that the administration of oral selenium solution to patients with selenium deficiency diseases, such as SMID, and patients under long-term total parenteral nutrition, thus improved the serum selenium concentration and GPx activity.

Formulation and evaluation of a folic acid receptor-targeted oral vancomycin liposomal dosage form.

To demonstrate utility of folic acid-coated liposomes for enhancing the delivery of a poorly absorbed glycopeptide, vancomycin. via the oral route. Liposomes prepared as dehydration-rehydration vesicles (DRVs) containing vancomycin were optimized for encapsulation efficiency and stability. A folic acid-poly(ethylene oxide)-cholesterol construct was synthesized for adsorption at DRV surfaces. Liposomes were characterized by differential scanning calorimetry (DSC) and assessed in vitro in the Caco-2 cell model and in vivo in male Sprague-Dawley rats. Non-compartmental pharmacokinetic analysis of vancomycin was conducted after intravenous and oral administration of solution or liposome-encapsulated vancomycin with or without 0.05 mole ratio FA-PEO-Chol adsorbed at liposome surfaces. Optimal loading of vancomycin (32%) was achieved in DRVs of DSPC:Chol:DCP, 3:1:0.25 mole ratio (m.r.) after liposome extrusion. Liposomes released less than 40% of the entrapped drug after 2 hours incubation in simulated gastrointestinal (GI) fluid and simulated intestinal fluid containing a 10 mM bile salt cocktail. Incorporation of FA-PEO-Chol in liposomes increased drug leakage by 20% but resulted in a 5.7-fold increase in Caco-2 cell uptake of vancomycin. Liposomal delivery significantly increased the area under the curve of oral vancomycin resulting in a mean 3.9-fold and 12.5-fold increase in relative bioavailability for uncoated and FA-PEO-Chol-coated liposomes, respectively, compared with an oral solution. The design of FA-PEO-Chol-coated liposomes resulted in a dramatic increase in the oral delivery of a moderate-size glycopeptide in the rat compared with uncoated liposomes or oral solution. It is speculated that the cause of the observed effect was due to binding of liposome-surface folic acid to receptors in the GI tract with subsequent receptor-mediated endocytosis of entrapped vancomycin by enterocytes.

Bioavailability of Etoposide after Oral Administration of the Solution Marketed for Intravenous Use: Therapeutic and Pharmacoeconomic Perspectives

Background Oral etoposide administration is a suitable alternative to the intravenous route; therefore, commercial capsules have been developed. Before these capsules were available in Mexico, we studied drug bioavailability after oral administration of the intravenous etoposide solution (IVES). Methods Eight adult cancer patients received a 50-mg oral etoposide dose as IVES and blood samples were collected over a period of 24 h. Plasma etoposide concentration was determined by high-performance liquid chromatography, plasma concentration against time curves were constructed, and bioavailability parameters were calculated. Results Oral IVES yielded an adequate bioavailability profile because C max was 2.38 ± 0.30 μg/mL, AUC was 12.87 ± 2.02 μg/mL and half-life was 6.72 ± 0.97 h. Conclusions Considering that the pharmacokinetic aim is to maintain plasma concentrations between 0.5 and 1.0 μg/mL for several hours while avoiding high concentrations, i.e., of 10 μg/mL or higher, oral administration of 50-mg etoposide as IVES appears to be a suitable dosing option. In addition, oral IVES is considerably less expensive than intravenous administration in terms of both drug presentation and administration.

Ultrasonography of the small bowel after oral administration of anechoic contrast solution

With transabdominal ultrasonography (US) it is not possible to thoroughly visualise the small interstinal loops that have a virtual lumen and may contain air; to our knowledge there are no reports of the US appearances of the entire small bowel except for sonographic descriptions of alterated findings, mainly at the level of the terminal i l e u m . , 2 However, as with the stomach and the large b o w e l , , 4 the walls of the small bowel may become visible by US when the lumen is distended with anechoic fluid. We have tested whether oral administration of a solution containing polyethylene glycol, which is not absorbed or f e r m e n t e d , can sufficiently distend the lumen of the small bowel and be used to perform small intestinal contrast ultrasonography (SICUS). Sal 38B and Tosbee equipment with 4 MHz and 5 MHz linear array transducers (Toshiba, Japan) were used to perform US in six healthy non-obese controls (two men, age range 26–47 yr) and in 31 (19 women, age 16–55 yr) consecutive patients with diagnostic suspicion of small bowel pathology. The US contrast isosmolar solution was obtained dissolving PEG 4000 29·2 g, anhydrous sodium sulphate 2·84 g, sodium bicarbonate 0·84 g, sodium chloride 0·72 g, and potassium chloride 0·36 g (Promefarm; Milan, Italy) in 500 mL of water. A US assessment of the entire abdomen was done after an