Biomedical subjects

I W Chen

Publications and source records attributed to I W Chen.

At least 37 records · Page 2Linked to original sources

PubMed1996

Improved oral absorption of L-365,260, a poorly soluble drug.

L-365,260, a specific and potent nonpeptide antagonist of the CCKB receptor, is under investigation for its potential utility in the treatment of anxiety and panic disorders. This drug has a very low aqueous solubility (< 2 micrograms mL-1). When L-365,260 was given orally as a suspension in 0.5% methylcellulose (5 mg kg-1), the absorption was rapid but incomplete. The peak concentrations occurred in about 30-40 min, and the bioavailability was 8.6% for the dog and 13.6% for the rat. The poor bioavailability could be attributed to poor absorption or extensive first-pass metabolism. By comparing the drug concentrations in the systemic circulation during portal and femoral (or cephalic) vein infusion, the hepatic first-pass metabolism was estimated to be 0.30 for the rat and 0.14 for the dog, suggesting that first-pass metabolism is not the main reason for the low bioavailability of the drug in rats and dogs. The limited bioavailability is, therefore, more likely due to its poor absorption as a result of its poor aqueous solubility and slow dissolution rate. However, while the absorption was substantially improved when the drug was given orally as a solution in PEG 600 solution, the bioavailability increased threefold to fourfold in rats and sixfold to sevenfold in dogs. Although the underlying mechanism for the improved absorption is unknown, PEG 600 may have exerted a cosolubilizing effect which enhances the dissolution rate of L-365,260 in the GI tract, resulting in better absorption. Kinetic analysis by a deconvolution technique revealed that PEG 600 increased both the extent and rate of absorption. These results are consistent with the notion that absorption of L-365,260 is rate limited by its dissolution rate. The data from these animal studies provides valuable information in selecting the formulation for clinical trials.

Absorption↗

PubMed1996

Species differences in the pharmacokinetics and metabolism of indinavir, a potent human immunodeficiency virus protease inhibitor.

Indinavir, a potent and specific inhibitor of human immunodeficiency virus protease, is undergoing clinical investigation for the treatment of acquired immunodeficiency syndrome. The studies described herein were designed to characterize the absorption, distribution, metabolism, and excretion of the drug in rats, dogs, and monkeys. Indinavir exhibited marked species differences in elimination kinetics. The plasma clearance was in the rank order: rat (107 ml/min/kg) > monkey (36 ml/min/kg) > dog (16 ml/min/kg). Significant differences in the bioavailability of indinavir also were observed. When given orally as a solution in 0.05 M citric acid, the bioavailability varied significantly from 72% in the dog to 19% in the monkey, and 24% in the rat. These differences in bioavailability were attributed mainly to species differences in the magnitude of hepatic first-pass metabolism. The distribution of indinavir was studied only in rats, both intravenously and orally. Intravenously, indinavir was distributed widely throughout the body. Brain uptake studies showed that indinavir penetrated the blood-brain barrier, but that the penetration was limited. After oral administration, indinavir was distributed rapidly into and out of the lymphatic system. The rapid lymph transfer is of clinical relevance, because a primary clinical hallmark of acquired immunodeficiency syndrome is the depletion of CD4 lymphocytes. Biliary and urinary recovery studies revealed that metabolism was the major route of indinavir elimination in all species, and N-dealkylation, N-oxidation, and hydroxylation seemed to be the major pathways. Although limited to qualitative aspects, the metabolite profile obtained from in vitro microsomal studies generally reflected the in vivo oxidative metabolism of indinavir in all species studies. Results from the chemical and immunochemical inhibition studies indicated the possible involvement of isoforms of the CYP3A subfamily in the oxidative metabolism of indinavir in rats, dogs, and monkeys. This is consistent with our previous studies, which have shown that CYP3A4 is the isoform responsible for the oxidative metabolism of indinavir in human liver microsomes. Furthermore, the in vivo oxidative metabolism of indinavir in rats, dogs, and monkeys was qualitatively similar to that in humans. The high degree of similarity in the metabolite profiles of drug metabolism between animals and humans validates the use of these animal models for toxicity studies of indinavir. Attempts were made to quantitatively extrapolate in vitro metabolic data to in vivo metabolism. With the application of the well-stirred and parallel-tube models, the hepatic clearance and hepatic extraction ratio were calculated using the in vitro Vmax/Km values. In rats, the predicted hepatic clearance (31 ml/ min/kg) and hepatic extraction ratio (0.47) agreed well with the observed in vivo hepatic clearance (43 ml/min/kg) and hepatic extraction ratio (0.68). In addition, the hepatic clearance of indinavir was predicted reasonably well in dogs and monkeys. Based on the in vitro intrinsic clearance of human liver microsomes, a small but significant hepatic first-pass metabolism (ca. 25%) is expected in humans.

Animals↗

PubMed1996

Sex-dependent pharmacokinetics of indinavir: in vivo and in vitro evidence.

Indinavir, a potent and specific inhibitor of human immunodeficiency virus protease, is used for the treatment of AIDS. This study was designed to investigate the sex-related differences in kinetics and metabolism of indinavir in rats, dogs, and monkeys to support the toxicity studies. When given intravenously, indinavir was cleared rapidly in a polyphasic manner in all species. Indinavir exhibited significant differences in elimination kinetics among species. The rat had the highest plasma clearance (CLp; 41-89 ml/min/kg), and the dog had the lowest CLp (15-26 ml/min/kg), with the monkey exhibiting an intermediate value (36-39 ml/min/kg). Furthermore, marked sex-related differences in CLp were observed in rats and dogs, but not in monkeys. The CLp was 89 ml/min/kg for male rats and 41 ml/min/kg for female rats. In contrast to rats, female dogs cleared indinavir more rapidly than male dogs; the CLp was 26 ml/min/kg for female dogs and 15 ml/min/kg for male dogs. Consistent with the in vivo observations, hepatic microsomes from male rats had a substantially higher metabolizing activity toward indinavir than that from females, whereas liver microsomes from female dogs catalyzed the drug at a higher rate than that from male dogs. Qualitatively, in vitro metabolic profiles of indinavir were similar among species and between male and female animals. Studies with an anti-rat cytochrome P450 (CYP) 3A1 antibody pointed to the probable involvement of isoforms in the CYP3A subfamily in the oxidative metabolism of indinavir in both males and females of all species. The functional activity of CYP3A measured by the formation of testosterone 6beta-hydroxylation and immunoblot analysis of the level of CYP3A proteins strongly suggested that gender differences in the levels of CYP3A isoforms may contribute to the observed sex-related differences in indinavir metabolism in rats and dogs.

Animals↗

PubMed1995

High-performance liquid chromatographic determination of a potent and selective HIV protease inhibitor (L-735,524) in rat, dog and monkey plasma.

A high-performance liquid chromatographic method coupled with liquid-liquid sample extraction and ultraviolet detection has been developed for the quantification of L-735,524 (I), a potent, highly selective and orally bioavailable inhibitor of recombinant human immunodeficiency virus (HIV) protease in rat, dog and monkey plasma. The present method is reproducible and reliable with limits of quantification of 25, 12.5 and 6.25 ng/ml, respectively for rat, dog and monkey plasma. The standard curve was linear over the range of 6.25-2000 ng/ml in the biological fluid. The mean coefficients of variation for concentration within the range of standard curve were 7.94, 6.91 and 4.52%, respectively, for intra-day analysis and 5.58, 9.27 and 5.45%, respectively, for inter-day analysis. The recoveries of I and L-707,943 (II), an analog of I used as the internal standard, from plasma samples were all over 88% through the extraction procedure. I and II are stable in mobile phase over a 48-h period while waiting for injection at ambient temperature and over a 144-h period in rat, dog and monkey plasma while stored at -20 degrees C. Aqueous solubility of I is pH dependent, 60 mg/ml at pH 3.5 and 0.3 mg/ml at pH 4.8. The analytic procedures described in this report have been successfully employed to quantify the concentration of I in rat, dog and monkey plasma and provide the kinetic information for toxicological and pharmacological studies.

Administration, Oral↗

PubMed1995

Regiospecific intestinal absorption of the HIV protease inhibitor L-735,524 in beagle dogs.

PURPOSE: To evaluate regional intestinal absorption and the feasibility of sustained release dosage form development for an HIV protease inhibitor, L-735,524, METHODS: L-735,524 free base or sulfate salt was administered orally as suspension, solution or in solid dosage forms to fasted or fed Beagle dogs. Delayed-release dosage forms with "slow" or "fast" in vitro dissolution rates were evaluated in vivo to assess plasma concentration profiles. In addition, drug was administered directly into the jejunum or colon of animals, and drug concentrations determined in portal circulation to characterize absorption from these sites. RESULTS: L-735,524 sulfate was well absorbed orally form a solution or capsule formulation if fasted animals' stomachs were preacidified with citric acid solution. A free base suspension, delivered in divided doses to fed animals, was also well absorbed. Prototype extended release dosage forms of L-735,524 produced a reduction in peak plasma levels but failed to prolong absorption and extend plasma concentrations compared to an immediate release capsule. Administration of L-735,524 sulfate solution (pH < 3) as bolus solution or by infusion into the jejunum resulted in rapid but incomplete absorption compared to oral gavage. The free base suspension (pH 6.5) delivered into jejunal or colonic regions did not produce measurable systemic plasma concentrations. CONCLUSIONS: Extended release formulations did not prolong absorption of L-735,524 in dogs. Optimal L-735,524 absorption was dependent on solubility in an acidic environment in the duodenum.

Administration, Oral↗

PubMed1995

pH-dependent oral absorption of L-735,524, a potent HIV protease inhibitor, in rats and dogs.

L-735,524, a potent and specific inhibitor of human immunodeficiency virus protease, is currently under investigation for the treatment of acquired immunodeficiency syndrome. The aqueous solubility of L-735,524 was pH-dependent, > 100 mg/ml at pH below 3.5 and 0.03 mg/ml at pH 6. When L-735,524 was given orally as a suspension in 0.5% methocel (pH 6.5) at 10 mg/kg, the bioavailability was approximately 16% for both dogs and rats. When the same dose of the drug was administered in 0.05 M citric acid (pH 2.5), the bioavailability increased 4.5-fold in dogs (72%), but only slightly in rats (24%). The pH- and species-dependent differences in bioavailability observed in rats and dogs may be because of differences in the rate of gastric acid secretion and in the magnitude of hepatic first-pass effect. Gastric acid secretion is poor in dogs but substantial in rats. When L-735,524 was administered in 0.5% methocel, a large portion of the drug in dogs, but not in rats, remained undissolved, resulting in poor absorption in dogs. On the other hand, when L-735,524 was administered in citric acid, most of the drug would be in solution allowing for better absorption in dogs. The hypothesis of pH-dependent absorption was further supported by the findings that absorption was significantly increased in dogs after feeding, but substantially decreased in rats after pretreatment with famotidine, a potent H2-receptor antagonist. L-735,524 underwent an extensive first-pass metabolism in rats, but not in dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1995

Time- and dose-dependent pharmacokinetics of L-754,394, an HIV protease inhibitor, in rats, dogs and monkeys.

L-754,394 is a potent and specific inhibitor of the HIV-1 encoded protease that is essential for the maturation of the infectious virus. The drug exhibited dose-dependent kinetics in all species studied (rat, dog and monkey); the apparent clearance decreased when the dose was increased. However, the dose-dependency cannot be explained by Michaelis-Menten kinetics. L-754,394 in plasma declined log-linearly with time, but with an apparent half-life that increased with dose. The apparent terminal half-life of L-754,394 in rats increased from 20 min at 0.5 mg/kg i.v. to 118 min at 10 mg/kg i.v. Furthermore, L-754,394 exhibited time-dependent pharmacokinetics. After chronic i.v. doses for 7 days (1 mg/kg/dose/day), the apparent clearance of L-754,394 in rats decreased from 87 ml/min/kg after the first dose to 25 ml/min/kg after the last dose. Similar results were observed in dogs and monkeys. In vitro spectral studies indicated that approximately 40 to 60% of the content of cytochrome P-450 was inactivated when L-754,394 (10 microM) was incubated with rat, dog and monkey liver microsomes in the presence of NADPH. Little or no inactivation of cytochrome P-450 was observed when either NADPH or L-754,394 was omitted. In addition, L-754,394 selectively inhibited CYP 2C11-dependent testosterone 2 alpha- and 16 alpha-hydroxylase activity and CYP 3A1/2-dependent testosterone 6 beta-hydroxylase activity, but not CYP 2D1/2-dependent bufuralol 1'-hydroxylase activity nor CYP 1A2-dependent phenacetin O-deethylase activity in rat liver microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1995

Metabolites of L-735,524, a potent HIV-1 protease inhibitor, in human urine.

L-735,524, N-[2(R)-hydroxy-1(S)-indanyl]-5-(2(S)-(1,1- dimethylethylaminocarbonyl)-4-[(pyridin-3-yl)methyl]piperazin++ +-1-yl)-4(S)- hydroxy-2(R)-phenylmethylpentanamide, is a potent and specific inhibitor of the human immunodeficiency virus type 1 protease and is undergoing clinical evaluation. In an initial clinical study, noninfected male volunteers were administered single, 1000 mg oral doses of nonlabeled compound. Urine samples were collected over a period of 48 hr. Metabolic profile of the urine was determined by HPLC-UV comparison with that from a human liver slice incubation of radiolabeled L-735,524. Seven significant metabolites were isolated from pooled human urine, and were characterized by NMR, MS, and/or chromatographic comparisons with authentic standards. The major metabolic pathways were identified as: a) glucuronidation at the pyridine nitrogen to yield a quaternized ammonium conjugate, b) pyridine N-oxidation, c) para-hydroxylation of the phenylmethyl group, d) 3'-hydroxylation of the indan, and e) N-depyridomethylation. A minor product was identified as 2',3'-trans-dihydroxyindan analog. Urinary excretion of L-735,524 and its metabolites represented a minor pathway of elimination. The intact parent compound seemed to be the major component in the urine, whereas the level of each metabolite was relatively low.

Chromatography, High Pressure Liquid↗

PubMed1994

On the absorption of alendronate in rats.

Alendronate is an antiosteolytic agent under investigation for the treatment of a number of bone disorders. Since the compound is a zwitterion with five pKa values and is completely ionized in the intestine at the physiological pH, absorption is poor; less than 1% of an oral dose is available systemically in rats. In the present studies, absorption was found to be predominantly in the upper part of the small intestine. Administration of buffered solutions of alendronate (pH 2-11) did not improve absorption. Whereas food markedly impaired the absorption of alendronate, EDTA enhanced absorption in a dose-dependent manner. Pretreatment of rats with ulcerogenic agents, mepirizole, acetylsalicylic acid, or indomethacin, resulted in a 3-7-fold increase in the oral absorption of alendronate. The absorption of phenol red, added as an indicator of intestinal tissue damage, was also increased in rats with experimental peptic ulcers. The enhanced absorption of alendronate observed in rats with experimental peptic ulcers was attributed to the alteration of the integrity of the intestinal membrane.

Administration, Oral↗

PubMed1994

Blood-brain barrier permeability and in vivo activity of partial agonists of benzodiazepine receptor: a study of L-663,581 and its metabolites in rats.

L-663,581 [FG 8205; 7-chloro-4,5-dihydro-5-methyl-3-(5-(1-methylethyl)- 1,2,4-oxadiazol-3-yl)6H-imidazo(1,5-A)(1.4)-benzodiazepine-6-one] is an investigational partial agonist of benzodiazepine receptors for possible application in the treatment of anxiety. Previous studies have shown that the drug is eliminated mainly by biotransformation in rats, dogs and monkeys. Two metabolites, mono- and bis-hydroxy analogs were demonstrated to be active in vitro. The potency of benzodiazepine receptor binding (Ki) is 3.7 nM for the parent drug, 3.3 nM for the mono-hydroxylated metabolite and 1.2 nM for the bishydroxylated metabolite, respectively. Although the metabolites are as potent as, or more so than the parent drug in vitro, they are inactive in rats in a conditioned emotional response model. This study was designed to explore the underlying mechanisms responsible for the discrepancy between in vitro and in vivo activity of the metabolites. After i.v. administration of L-663,581 or its preformed metabolites, the metabolites were cleared more slowly than the parent drug. After i.p. administration at the same dose, the areas under the curve of the metabolites were 2 to 5 times that of the parent drug. Thus, the lack of in vivo activity of the metabolites cannot be explained by the absorption and/or elimination kinetics. Brain uptake studies indicated that the permeability of the blood-brain barrier is high for L-663,581 but very poor for the metabolites; the brain extraction ratio was about 0.6 for L-663,581 and less than 0.03 for the metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Role of calcium in plasma protein binding and renal handling of alendronate in hypo- and hypercalcemic rats.

Alendronate (4-amino-1-hydroxybutylidine-1,1-bisphosphonate), an antiosteolytic agent, is currently under investigation for the treatment of osteoporosis. Earlier studies in animals from this laboratory disclosed that systemically administered alendronate is rapidly taken up by bone tissues to the extent of 60% to 70% of the dose and excreted by the kidney, 30% to 40% in 24 hr, and that renal excretion is the only route of elimination. This study was designed to explore the effect of calcium on plasma protein binding and the renal handling of alendronate. The binding of alendronate to rat plasma was concentration, pH and calcium dependent. The fraction of unbound drug in rat plasma increased from about 3% to 9% over a drug concentration range of 0.2 to 10 micrograms/ml. Supplementation of calcium strongly augmented the binding to serum albumin. The binding of alendronate in plasma increased with increasing pH from about 50% at pH 6.6 to 98% at pH 8.6. The effects of pH on the binding of calcium and of alendronate to serum albumin were qualitatively similar. Under steady-state conditions, the binding of alendronate was substantially lower in hypocalcemic rats but unchanged in hypercalcemic rats. Although hypocalcemia caused a significant decrease in the renal secretion of alendronate, there was no effect on the renal secretion of tetraethylammonium bromide and p-aminohippuric acid. The differential effect of hypocalcemia suggests that calcium may play an important role in the renal handling of alendronate. However, hypercalcemia resulted in a substantial decrease of renal secretion of all three compounds and the decreased renal secretion was associated with a marked decrease in the glomerular filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Alendronate↗

PubMed1992

Quantitation of a new cholecystokinin and gastrin receptor antagonist (L-365,260) in dog and rat plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) procedure has been developed for the quantification of L-365,260 (I), a cholecystokinin and gastrin receptor antagonist, in dog and rat plasma. The method involves liquid-liquid extraction and HPLC with ultraviolet detection. Standard curves were linear over the range 7.5-2000 ng/ml for rat and dog plasma. The method is reproducible and reliable with a detection limit of 7.5 ng/ml in biological fluids. The mean coefficients of variation for concentrations within the range of the standard curve range were 3.84 and 2.56%, respectively, for intra-day analysis and 4.48 and 4.26%, respectively, for inter-day analysis. Application of the development was successfully demonstrated by quantifying the concentration of I in both dog and rat plasma samples following an intravenous or oral dose of 5 mg/kg I.

Animals↗

PubMed1992

Dose-dependent toxicokinetics of L-689,502, a potent human immunodeficiency virus protease inhibitor, in rats and dogs.

L-689,502, N-[2(R)-hydroxy-1(S)-indanyl]-5(S)-(1,1-dimethylethoxy- carbonylamino)-4(S)-hydroxy-6-phenyl-2(R)-(4-[2-(4- morpholinyl)ethoxy]phenyl)methyl hexanamide, is a potent inhibitor of human immunodeficiency virus-1 protease. The effect of dose on the elimination kinetics of L-689,502 was studied in rats and dogs. After i.v. administration, total plasma clearance of L-689,502 in rats decreased with increasing dose; the clearance decreased from 181 ml/min/kg at 1 mg/kg to 86 ml/min/kg at 20 mg/kg. Similar results were observed in dogs; clearance fell from 29 ml/min/kg at 0.5 mg/kg to 17 ml/min/kg at 10 mg/kg. Bile flow in rats was retarded in a dose-dependent manner after a single i.v. injection of L-689,502. The cholestatic effect was reversible and maximal at 5 mg/kg i.v. Consistent with the cholestatic effect, L-689,502 caused an increase in serum levels of aminotransferase. After i.v. administration of L-689,502 (10 mg/kg), alanine aminotransferase increased from 50 to 370 IU/liter and aspartate aminotransferase from 120 to 700 IU/liter. Moreover, pretreatment of rats with L-689,502 resulted in a significant decrease in the elimination kinetics of antipyrine and diflunisal, as well as of L-689,502 itself. Collectively, these results suggest that the dose-dependent kinetics of L-689,502 in rats and dogs are more likely due to hepatotoxicity caused by the drug than to capacity-limited metabolism.

Acetaminophen↗

PubMed1991

Dose-dependent pharmacokinetics of MK-417, a potent carbonic anhydrase inhibitor, in experimental polycythemic and anemic rats.

MK-417 is a potent carbonic anhydrase inhibitor currently under clinical investigation as a topical ocular hypotensive agent. While present in most of the tissues, carbonic anhydrase predominates in red blood cells. Earlier studies from our laboratory have demonstrated that carbonic anhydrase plays an important role in the elimination kinetics of MK-417 and that the enzyme can be saturated when MK-417 exceeds the stoichiometric concentration of the enzyme. Since carbonic anhydrase is an intracellular enzyme in erythrocytes, conditions which may change the hematocrit can alter the load of MK-417 needed to saturate carbonic anhydrase. It is, therefore, important to determine the effects of anemic and polycythemic states on the pharmacokinetics of MK-417. The anemic state in rats was obtained by replacing whole blood with donor plasma (12-15 ml), while polycythemia was induced by infusion of 12 to 15 ml of whole blood. At low doses (0.05 and 0.1 mg/kg), the pharmacokinetic parameters for MK-417 remained unchanged and there were no significant differences in the pharmacokinetic parameters among the anemic, polycythemic, and normal rats. The total blood clearance and apparent volume of distribution were increased markedly when the dose exceeded 0.2 mg/kg in anemic rats and 0.5 and 1 mg/kg in normal and polycythemic rats, respectively. Clearly, the dose of MK-417 required to saturate the enzyme was different among the three groups of animals. However, the terminal half-life was dose independent and not influenced by hematocrit.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗

PubMed1990

High-performance liquid chromatographic determination of cilastatin and its major metabolite N-acetylcilastatin in rat plasma, urine and bile.

A new high-performance liquid chromatographic method coupled with solid-phase (C8) sample extraction has been developed for the simultaneous quantification of cilastatin and its major metabolite N-acetylcilastatin in rat plasma, urine and bile. The method is linear, reproducible and reliable with a detection limit of 1 microgram/ml in all three fluids. Plasma concentrations of cilastatin and N-acetylcilastatin at selected time intervals and biliary and urinary recoveries of cilastatin and N-acetylcilastatin following an intravenous dose of 10 mg/kg cilastatin are presented.

Animals↗

PubMed1990

Serum osteocalcin measurements in prostate carcinoma patients with skeletal deposits shown by bone scintigram: comparison with serum PSA/PAP measurements.

The correlation of technetium-99m-HMDP bone scintigraphic findings, serum osteocalcin as a measure of bone turnover and prostate-specific antigen (PSA) and/or prostate acid phosphatase (PAP) was determined in 19 men with bone metastasis due to prostatic carcinoma. Six of the 19 patients with metastases on bone scan showed elevation of osteocalcin. These patients had extensive metastatic disease. All 19 men with positive bone scans had high serum PSA and/or PAP levels. Serum osteocalcin measurement is less sensitive to detection of bone deposits than PSA/PAP measurements (p less than 0.0008).

Acid Phosphatase↗

PubMed1990

[Investigation on the relation between hepatitis B virus knowledge and needle-stick injury of hospital personnel].

The purposes of this study are: (1) to understand the knowledge of Hepatitis B virus known by hospital personnel. (2) to investigate the injury caused by accidental needle stick and its frequency. (3) to identify those personnel and job activities at high risk of needlestick injuries, to assess current medical management of these injuries in our hospital, and also to develop rational guidelines for prevention, based on the findings. 510 effective questionnaires were collected and analyzed by SPSS analytical system. The result of the present study showed that 77.1% hospital personnel had been experienced by needlestick injury. Most injuries occurred during recapping the needle after use and disposal of used needle. 92.7% hospital personnel felt that hospital should provide all the expense needed for Hepatitis B virus immunoglobulin while needle-stick injuries happened within the hospital. 86.3% of them felt that hospital should establish a special committee to evaluate and manage all the needle-stick injuries events. This study also showed that hospital personnel who have been working less than five years and their age between 21-30 can pay more attention to this kind of event. Dietitian and doctor got higher score in this study. Hospital personnel who were infected by Hepatitis B virus scored higher than uninfected one. In conclusion, we recommend not recapping used needles and making widely available and promoting use of an efficient needle disposal system. And we hope that those who have never been infected by Hepatitis B virus should accept vaccination as soon as possible.

Accident Prevention↗

PubMed1988

Hematoporphyrin derivative uptake and photodynamic therapy in pancreatic carcinoma.

Little information is currently available concerning the uptake of porphyrins by pancreatic tumors, or the effect of photodynamic therapy (PDT) on pancreatic cancer. In Syrian golden hamsters (n = 33), the organ distribution of 125I-labeled dihematoporphyrin ether (DHE) was studied in a pancreatic cancer model. In the same animal model the effect of PDT was studied using a gold vapor laser for energy delivery 3 hr after the injection of DHE (n = 7). DHE was 2.4 times more concentrated in the pancreatic tumor than in the nontumorous pancreas at 3 hr. Simultaneously there was a considerable accumulation of DHE in the surrounding gastrointestinal tract, causing perforation of the duodenum and jejunum with resultant death in four (57%) animals after PDT. Photodynamic therapy caused extensive tumor necrosis without any obvious effect on the nontumor-bearing pancreas. Damage to the surrounding tissue in the hamster indicates that precautions should be taken if PDT is to be used clinically in pancreatic cancer. Intratumoral injection of DHE may give higher drug concentrations with greater specificity for tumor treatment.

Adenocarcinoma↗