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C Larsen

Publications and source records attributed to C Larsen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Modification of in vitro drug release rate from oily parenteral depots using a formulation approach.

Rate constants for transfer of naproxen and lidocaine from different oils and oil mixtures to aqueous buffer, pH 6.00, were determined using the rotating dialysis cell. Significantly different first-order rate constants related to attainment of equilibrium, k(obs), were derived depending on the type of oil/oil mixtures used in the release experiments. For the drugs a linear correlation was found between logk(obs) and the logarithm of the partition coefficient P(app): logk(obs)=-0.68 logP(app)-0.25 (k(obs) in h(-1), n=26). A linear relationship was observed between the calculated and experimentally determined P(app) values for the oil mixtures investigated. The specific rate constants, k(ow) and k(wo), related to the partition process were derived from the determined k(obs) and P(app) values. The rate constant k(ow) representing the rate of transfer of the solute from the oil phase to the aqueous buffer was shown to be strongly dependent on the partition coefficient according to the relationship: logk(ow)=-0.68 logP(app)-log(P(app)+1)-0.25 (k(ow) in h(-1), n=26). In particular, diminished release rates were seen for oil mixtures containing castor oil most likely afforded by hydrogen bonding between the solute and the hydroxy groups of the latter vegetable oil. In this study it has been possible to alter P(app) for a specific compound up to a factor of 10 by variation of the composition of the oil vehicle. Such a span of P(app) values results in in vitro release rates differing a factor of 37. Thus, by proper design of the oil vehicle composition it should be possible to modify the release rate for a specific compound within certain limits.

Castor Oil↗
PubMed2000

Assessment of rate of drug release from oil vehicle using a rotating dialysis cell.

The rate constants for transfer of model compounds (naproxen and lidocaine) from oily vehicle (Viscoleo) to aqueous buffer phases were determined by use of the rotating dialysis cell. Release studies were done for the partly ionized compounds at several pH values. A correlation between the overall first-order rate constant related to attainment of equilibrium, k(obs), and the pH-dependent distribution coefficient, D, determined between oil vehicle and aqueous buffer was established according to the equation: logk(obs)=-0.71 logD-0.22 (k(obs) in h(-1)). Based on this correlation it was suggested that the rate constant of a weak electrolyte at a specified D value could be considered equal to the k(obs) value for a non-electrolyte possessing a partition coefficient, P(app), the magnitude of which was equal to D. Specific rate constants k(ow) and k(wo) were calculated from the overall rate constant and the pH-dependent distribution coefficient. The rate constant representing the transport from oily vehicle to aqueous phase, k(ow), was found to be significantly influenced by the magnitude of the partition coefficient P(app) according to: logk(ow)=-0.71 logP(app)-log(P(app)+1)-0.22 (k(ow) in h(-1)).

Coconut Oil↗
PubMed1999

Metabolism and excretion of citalopram in man: identification of O-acyl- and N-glucuronides.

The antidepressant citalopram (CT), a selective serotonin uptake inhibitor, was given in its labelled form, [14C]-CT, as a single oral dose in 50 ml aqueous solution (0.1 mmol/30 microCi/1.1 MBq) to four healthy male volunteers. Concentrations of radioactivity in whole blood and plasma were similar. The respective pharmacokinetic parameters were: Cmax = 214+/-41 and 246+/-69 nmol eq./litre, Tmax = 3 and 2 h, AUC = 18289+/-2959 and 14537+/-2883 nmol eq. h/litre, and t1/2 = 90.2+/-22.5 and 79.5 +/- 14.9 h respectively. A mean of 85.2 +/- 10.4% of the radioactive dose was recovered after 17 days of collection of excreta. The majority of radioactivity was excreted in urine (74.7+/-8.9%) and the remaining part in faeces (10.5+/-2.3%). The HPLC profile of urinary components showed that besides the known metabolites of citalopram, three glucuronides were present. The relative amounts of CT and its metabolites in urine collected for 7 days were: CT (26 %), N-demethyl-CT (DCT, 19%), N,N-didemethyl-CT (DDCT,9%), the N-oxide (7%), the quaternary ammonium glucuronide of CT (CT-GLN, 14%), the N-glucuronide of DDCT (DDCT-GLN, 6%), and the glucuronide of the acid metabolite (CT-acid-GLN, 12%) formed by N,N-dimethyl deamination of CT. CT-GLN was isolated using preparative chromatography and identified by LC-MS-MS and NMR. DDCT-GLN and CT-acid-GLN were identified by LC-MS. This study shows that protracted renal excretion represents the major route of elimination, with a small fraction voided with faeces. A considerable portion of the urinary excreted dose consists of N-glucuronides of CT and DDCT together with the O-acyl glucuronide of CT-acid.

Acylation↗
PubMed1997

Rotating dialysis cell as in vitro release method for oily parenteral depot solutions.

The purpose of the study was to investigate an in vitro release method based on a rotating dialysis cell for parenteral oil depot formulations using different model conditions and test formulations. The total amount of drug released from the rotating dialysis cell was in accordance with the theoretical values calculated from the partition coefficients. The release rates were shown to depend on the total amount of drug available for the release process and to follow first order kinetics. The rotating dialysis cell has a potential as in vitro release method for characterization of oily depot formulations for parenteral administration.

Journal Article↗
PubMed1997

Comparison of the disposition of hepatically-generated morphine-3-glucuronide and morphine-6-glucuronide in isolated perfused liver from the guinea pig.

PURPOSE: Humans and guinea pigs metabolise morphine extensively, forming the isomers morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in relatively similar ratios. Both metabolites are formed in the liver, and their greater polarity relative to the parent aglycone may limit their permeability across hepatic membranes. This study compared the disposition of hepatically-generated M3G and M6G in perfused livers isolated from guinea pigs. METHODS: Livers were perfused at 30 ml/min in a non-recirculating manner with Krebs bicarbonate buffer containing morphine (6 to 7 microM). Perfusing medium, venous perfusate and bile were collected at regular intervals and concentrations of morphine, M3G and M6G determined by reversed-phase HPLC. RESULTS: Concentrations of morphine, M3G and M6G in perfusate and the rates of biliary excretion of M3G and M6G were consistent between 20 and 50 min of perfusion. The mean (+/-s.d.) ratio for the rate of formation of M3G relative to M6G was 3.7 +/- 1.5. A mean 33 +/- 3% of morphine extracted by the liver was recovered as summed M3G and M6G. Of the M3G and M6G formed during a single passage, 19 +/- 11% and 9 +/- 9%, respectively, was excreted into bile; the values were significantly different (P = 0.002). CONCLUSIONS: A greater fraction of hepatically-generated M3G excreted into bile compared to that for M6G reflects differences in their relative transport across sinusoidal and canalicular membranes of hepatocytes, possibly via carrier-mediated systems.

Analgesics, Opioid↗
PubMed1997

Setting the stage for health impact assessment.

Defining health impact assessment as any combination of procedures or methods by which a proposed policy or program may be judged as to the effect(s) it may have on the health of a population, we make recommendations about how to evaluate the health impact of all government-initiated policies. Such health impact cannot be assessed in the absence of a conceptual or organizing framework that provides the requisite guideposts--population health goals and targets. Health impact assessment offers an approach to ensuring that governments' program and policy initiatives align, or are congruent with, the agreed-upon health goals. It suggests that proposed national policies should be supported or resisted on the basis of their probable influence on the health of populations. In the current Canadian national policy framework, however, there are no underpinnings on which to situate such a process. The specification of consensus goals and objectives with measurable targets can provide the requisite guideposts and benchmarks for health impact assessment. Such an undertaking can set the stage and provide the necessary foundation for an effective health impact assessment process.

Canada↗
PubMed1995

Reductant-independent ATP hydrolysis catalyzed by homologous nitrogenase proteins from Azotobacter vinelandii and heterologous crosses with Clostridium pasteuranium.

Reductant-independent ATPase activity was initiated and studied for Azotobacter vinelandii and Clostridium pasteuranium nitrogenase proteins (Av1, Cp1 and Av2, Cp2, 1 designating the iron molybdenum protein and 2 the iron protein) and their heterologous crosses by two methods: (1) allowing dithionite to be depleted from a normal assay in the presence of substrate levels of MgATP and (2) using reduced but reductant-free nitrogenase proteins in the presence of substrate levels of MgATP. In both cases, at a 1:1 protein ratio, MgATP is converted initially to MgADP with a specific activity of 400-500 nmol MgATP hydrolyzed/min.mg Av1, but in slower steps the MgADP is converted to AMP and, after 12 h, AMP is ultimately converted to adenosine. This reactivity requires the presence of both proteins, increases with increasing Av2/Av1 ratio, and is not a result of unique redox states of either protein. For Av1-Av2, ATP hydrolysis in the absence of Mg2+ occurred at nearly the same rate as reductant-dependent MgATP hydrolysis. Reductant-independent ATPase activity also occurred for the Av1-Cp2 and Cp1-Av2 heterologous crosses and was 2-fold and 18-fold slower than the Av1-Av2 or Cp1-Cp2 combinations. In both cases further hydrolysis of MgADP to AMP and AMP to adenosine occurred. A unique nucleotide hydrolysis system is apparently operating in the complex formed between the two nitrogenase proteins in the absence of reductant. The relationship between the reductant-independent and reductant-dependent activities of nitrogenase catalysis is explored.

Adenosine Triphosphate↗
PubMed1995

Intraoperative ultrasonography in detection of hepatic metastases from colorectal cancer.

PURPOSE: This study was designed to compare diagnostic accuracies of measuring liver enzymes, preoperative ultrasonography, surgical examination, and intraoperative ultrasonography for detection of liver metastases from colorectal cancer. METHODS: Blind, prospective comparisons of diagnostic examinations mentioned above were performed in 295 consecutive patients with colorectal cancer. An experienced ultrasonologist performed the preoperative examinations, and results were unknown to the other experienced ultrasonologist who performed the intraoperative examinations. The latter, also was unaware of the findings by the surgeon. The presence of metastases was further assessed by ultrasonography three months postoperatively, as well as additional surgery and liver biopsy in some of the patients. RESULTS: The sensitivity of intraoperative ultrasonography (62/64) was significantly superior to that of surgical exploration (54/64) and that of preoperative ultrasonography (45/64). The lowest sensitivity was presented by liver enzymes. Bilobar metastases were detected in 42 of 46 patients by intraoperative ultrasonography but in only 33 patients by the surgeon. Intraoperative ultrasonography demonstrated the highest specificity of all examinations. CONCLUSIONS: Intraoperative ultrasonography reduces the number of patients with liver metastases from being subjected to superfluous or even harmful liver surgery, and it may increase the number in whom liver surgery will prolong life.

Adult↗
PubMed1995

Metal ion binding to apo, holo, and reconstituted horse spleen ferritin.

The binding of Cd2+, Zn2+, Cu2+, Ni2+, Co2+, Mn2+, and Mg2+ to apo, holo, reconstituted horse spleen ferritin (HoSF), and native holo HoSF with phosphate removed was measured by gel-exclusion chromatography. Three classes of strong binding interactions (Kd < 10(-7) M) with apo HoSF at pH 7.5 were found for the various M2+ studied: high stoichiometric binding (30-54 M2+/HoSF) for Cd2+, Zn2+, Cu2+, with two protons released per metal bound; intermediate binding (16 M2+/HoSF) for Ni2+ and Co2+, with one proton released per metal bound; and low levels of binding (2-12 M2+/HoSF) for Mn2+, Mg2+, and Fe2+, with < 0.5 protons released per metal bound. M2+ binding to apo HoSF was nearly abolished at pH 5.5, except for Fe2+ and Cu2+, which remained unaffected by pH alteration. Holo HoSF bound much higher levels of M2+, a result directly attributable to the presence of phosphate binding sites. This conclusion was confirmed by decreased binding of M2+ to HoSF reconstituted in the absence of phosphate and by native holo HoSF with phosphate chemically removed. The binding of Cd2+ to apo HoSF was 54 per HoSF, but in the presence of developing core, the amount bound decreased to about 30 Cd2+/HoSF. This result indicated that Cd2+ and developing core were competing for the same sites on the HoSF interior, suggesting that 24 of the Cd2+ were bound to the inside surface. No other M2+ studied bound to the interior of HoSF by this criterion. Several of the M2+ appeared to bind strongly to the phosphate-free mineral core surface in reconstituted HoSF.

Animals↗
PubMed1994

Use of iotrolan versus ethiodized poppy-seed oil in hysterosalpingography.

PURPOSE: To compare use of the water-soluble, nonionic isosmolar dimer iotrolan with that of ethiodized poppy-seed oil in hysterosalpingography with regard to side effects, diagnostic quality, and postexamination conception rates. MATERIALS AND METHODS: A prospective randomized design was used in a study of 245 patients. Questionnaires and patient records were used to acquire information. All examinations and ratings of diagnostic quality were performed by the same three investigators. Statistical calculations were performed with the chi 2 test, including the Mantel-Haenszel variant, and the Kruskal-Wallis test. RESULTS: No substantial differences between the contrast media could be detected concerning pain during the procedure, delayed pain, or postexamination bleeding. Visualization of the uterine cavity and ampullary rugae was markedly better with use of iotrolan. The postexamination conception rate was higher with use of ethiodized poppy-seed oil (24.0%) but was not significantly different statistically (P = .44) from that seen after use of iotrolan (19.8%). CONCLUSION: The authors believe the use of iotrolan is preferable to that of ethiodized poppy-seed oil.

Abdominal Pain↗