Abstract:
:Oxycodone is an opioid analgesic that is administered orally or parenterally. The time-course of opioid action is a function of the systemic kinetics of the opioid, and the rate and extent of its entry into the brain and central nervous system. The latter is incompletely understood for oxycodone. Therefore, the cerebral kinetics of oxycodone was quantified using a conscious chronically instrumented sheep preparation. Five sheep were administered oxycodone as intravenous infusions (30 mg over 4 min). Using hybrid physiologically based kinetic models, cerebral kinetics was estimated from arterio-sagittal sinus concentration gradients and cerebral blood flow (CBF). A two-compartment membrane-limited model best described the data. The volume of the first brain compartment was 35.4 mL with a half-life of equilibrium of 0.6 min. The brain:blood equilibration of oxycodone was relatively slow (half-life of 7.2 min), with a large deep cerebral distribution volume (222.8 mL) for the second compartment and a moderate membrane permeability of 54.8 mL/min, which exceeded the nominal CBF (40 mL/min). Drug retention in the brain was 1.3% after 45 min. In conclusion, pharmacokinetic modelling of oxycodone showed a delayed equilibration between brain and blood of a nature that would be affected by changes in both CBF and blood brain barrier permeability.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Villesen HH,Foster DJ,Upton RN,Somogyi AA,Martinez A,Grant Cdoi
10.1002/jps.20632subject
Has Abstractpub_date
2006-08-01 00:00:00pages
1666-76issue
8eissn
0022-3549issn
1520-6017pii
S0022-3549(16)32071-8journal_volume
95pub_type
杂志文章abstract::The solubility equation of Yalkowsky was used to estimate the aqueous solubility of 33 barbiturates in the temperature range of 5 to 45 degrees C. The equation was extended by adding a term which accounts for the effect of pH on the solubility of the drug. The extended equation is successful in estimating the aqueous ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600760120
更新日期:1987-01-01 00:00:00
abstract::Human insulin exists in different association states, from monomer to hexamer, depending on the conditions. In the presence of zinc the "normal" state is a hexamer. The structural properties of 20 variants of human insulin were studied by near-UV circular dichroism, fluorescence spectroscopy, and small-angle X-ray sca...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10355
更新日期:2003-04-01 00:00:00
abstract::The synthesis of diazoketone analogs of amino acids and associated problems were investigated with N-phthaloyl-DL-alanine serving as a model. The carboxyl was activated by conversion to the acid chloride or, under mild conditions, to the mixed anhydride obtained with ethyl chloroformate or dicyclohexylcarbodiimide; th...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600670518
更新日期:1978-05-01 00:00:00
abstract::5-aminolevulinic acid (ALA) is used as a precursor of protoporphyrin IX (PpIX) for photodynamic therapy (PDT) of superficial skin cancers and subcutaneous metastases of internal malignancies. The permeability of ALA across intact skin is always low, making it difficult to achieve the desired therapeutic benefits. Henc...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20577
更新日期:2006-04-01 00:00:00
abstract::A single method for the quantitative determinations of three active ingredients, phenylephrine hydrochloride, phenylpropanolamine hydrochloride, and brompheniramine maleate, and one inactive ingredient (sodium benzoate) in a commercial product for colds is reported. The method is based on paired ion high-pressure liqu...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600670643
更新日期:1978-06-01 00:00:00
abstract::Ascorbic acid has a unique role in the prevention and treatment of a large number of chronic diseases, including skin disorders but it can hardly penetrate the skin due to its solubility in water and its high instability. This study explored the formation of phosphatidylcholine-based vesicles upon addition of ascorbyl...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2020.06.017
更新日期:2020-10-01 00:00:00
abstract::Iontophoretic transdermal delivery of sumatriptan was investigated in vitro. Among the conditions tested, 0.25 mA/cm2 and low ionic strength (NaCl 25 mM) was the best experimental condition to increase its transport across the skin. The flux increased 385-fold respective to passive diffusion, thus resulting in a trans...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20447
更新日期:2005-10-01 00:00:00
abstract::Cosalane is a potent inhibitor of HIV replication with multiple sites of action. The purposes of this study were to (a) determine the extent and nature of cosalane binding to mucin, alpha(1)-acid glycoprotein (AAG), plasma, and human (HSA) and bovine serum (BSA) albumin, and (b) determine the primary site(s) of cosala...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/1520-6017(200105)90:5<659::aid-jps1022>3.0
更新日期:2001-05-01 00:00:00
abstract::A rapid and sensitive GLC method was developed for the quantitative determination of methenamine in tablets. The method was shown to possess several advantages over the official NF assay. After dissolution of the whole tablet in absolute ethanol and addition of an internal standard (pentylenetetrazol), an aliquot was ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600660435
更新日期:1977-04-01 00:00:00
abstract::The purpose of this study was to evaluate the cardiovascular effects of two potential beta-hydroxylase inhibitors, a dithiocarbamate and a thiourea derivative of d-amphetamine, 1 and 2, respectively. These compounds when given intravenously elicited a significant dose-dependent depressor effect in normotensive rats an...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600740621
更新日期:1985-06-01 00:00:00
abstract::We investigate the presence of a surface species for the active pharmaceutical ingredient (API) AZD9496 with dynamic nuclear polarization surface enhanced nuclear spectroscopy (DNP SENS). We show that using DNP we can elucidate the presence of an amorphous form of the API at the surface of crystalline particles of the...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2020.12.037
更新日期:2021-01-05 00:00:00
abstract::The pharmacokinetics of valproic acid after oral administration of sustained-release formulations were studied in 12 healthy volunteers. The objective of the present study was to find an appropriate mathematical model to describe the complex drug intake process. The concentration of valproic acid in plasma was measure...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600831019
更新日期:1994-10-01 00:00:00
abstract::Within the last decade, Quality by Design (QbD) has been getting increased attention in its implementation in the development of pharmaceutical drug products. Understanding of the impact of formulation composition and process on clinical performance is a centerpiece of QbD. Physiologically based pharmacokinetic modeli...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2016.11.022
更新日期:2017-04-01 00:00:00
abstract::Volunteers were injected im with 100 mg of tripelennamine (pyribenzamine).HCl dissolved in saline. Timed urine was collected. Tripelennamine and its metabolites were identified by GC/MS. Amounts of free tripelennamine excreted in the 0-2-, 2-4-, 4-8-, 8-12-, and 12-24-h urine samples were found to be 0.30, 0.56, 0.17,...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600800902
更新日期:1991-09-01 00:00:00
abstract::Mixing Fungizone with a fat emulsion used for nutritional purpose (Intralipid or Lipofundin ) was reported to decrease Amphotericin B (AmB) toxicity in clinical use. In an effort to understand the reason for this phenomenon, spectral and morphological analyses were done for the Fungizone and Fungizone /Lipofundin admi...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10223
更新日期:2002-11-01 00:00:00
abstract::Prostaglandin F2 alpha was administered intraamniotically to 132 mid-first trimester gravidas to determine the dose-24-hour abortifacient response relationship. Single doses between 15-50 mg and multiple doses between 15-25 mg were administered to 3 groups each, the latter regimen at 6-hour intervals. Trials were de...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600620809
更新日期:1973-08-01 00:00:00
abstract::We describe the key issues and possibilities for continuous final dosage formation, otherwise known as downstream processing or drug product manufacturing. A distinction is made between heterogeneous processing and homogeneous processing, the latter of which is expected to add more value to continuous manufacturing. W...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1002/jps.24247
更新日期:2015-03-01 00:00:00
abstract::A kinetic dialysis technique together with a radiolabeled chenodeoxycholate (CDC) was used to determine the existence of a relationship between the monomer concentration of CDC and the total CDC concentration in different CDC solutions containing 1 or 5 mM sulfobutylether (SBE)-β-cyclodextrin. On the basis of the natu...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23231
更新日期:2012-08-01 00:00:00
abstract::(6R,7R)-7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-(Z)-2-methoxy- iminoacetamid]-3- [(4-carbamoyl-1-quinuclidinio)methyl]-8-oxo-5-thia-1-azabicyclo [4,2,0]oct-2-ene-2-carboxylate (1; E1040) was isolated as alpha-(decahydrate), beta-(pentahydrate), and gamma-form (anhydrate) crystals and the X-ray amorphous form. The relatio...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600781103
更新日期:1989-11-01 00:00:00
abstract::The results of studies on tedisamil dihydrochloride in the solid state demonstrate that the compound occurs in three polymorphic forms. The three modifications have been characterized by thermomicroscopy, differential scanning calorimetry (DSC), vibrational spectroscopy, solid-state nuclear magnetic resonance (NMR), a...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/1520-6017(200009)89:9<1151::aid-jps7>3.0.c
更新日期:2000-09-01 00:00:00
abstract::The blood-brain barrier permeation has been investigated by using a topological substructural molecular design approach (TOPS-MODE). A linear regression model was developed to predict the in vivo blood-brain partitioning coefficient on a data set of 119 compounds, treated as the logarithm of the blood-brain concentrat...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20081
更新日期:2004-07-01 00:00:00
abstract::A diffusion model for the percutaneous absorption of a solute through the skin is developed for the specific case of a constant donor concentration with a finite removal rate from the receptor due to either perfusion rate or sampling. The model has been developed to include a viable epidermal resistance and a donor-st...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js990053i
更新日期:1999-11-01 00:00:00
abstract::A simple enzyme immunoassay for the determination of captopril was developed. A specific antibody for captopril was produced in rabbits that were immunized with a hapten-bovine immunoglobulin G conjugate, which was prepared by using 4-(maleimidomethyl)cyclohexane carboxylic acid as a spacer group. The limit of detecti...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600750720
更新日期:1986-07-01 00:00:00
abstract::The single-dose pharmacokinetics and bioavailability of three ketoconazole formulations were evaluated using HPLC in five healthy human volunteers and six male mongrel dogs. The human volunteers received 400 mg po of ketoconazole as tablet (Ktab) and solution (Ksol) formulations. The dogs received 400 mg po of Ktab an...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600750504
更新日期:1986-05-01 00:00:00
abstract::Corneal permeability data taken from the literature were analyzed for possible quantitative relationships with physicochemical properties. Although a parabolic relationship was obtained with good correlation between lipophilicity, as expressed by the 1-octanol-water partition coefficients, log Poctanol (or the distrib...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js960076m
更新日期:1996-08-01 00:00:00
abstract::A tetrazole ring is often used in drug discovery as a replacement for the carboxylic acid group. Previous work indicates that compounds containing a tetrazole moiety show asymmetric permeability in Caco-2 cells characteristic of an efflux transporter substrate. The aim of this study is to determine which transporters ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20526
更新日期:2006-04-01 00:00:00
abstract::Small particles of two steroids, cholesteryl acetate and beta-sitosterol, were prepared by the following technique. The steroid was dissolved in an organic solvent, which was emulsified in water in the presence of surfactant, thus giving a water-continuous emulsion. As the organic solvent was evaporated, the steroid p...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600820608
更新日期:1993-06-01 00:00:00
abstract::A GLC determination of cyclobenzaprine in human plasma and urine is described. After extraction from alkalinized samples with heptane-isopentyl alcohol (97:3), the drug and internal standard were back-extracted into 0.1 N HCl and then reextracted into ether. Use of a lower homolog of the drug as an internal standard w...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600650832
更新日期:1976-08-01 00:00:00
abstract::A rapid solubility-screening assay was developed with a focus on Biopharmaceutic Classification Scheme (BCS) class II drug solubility in animal and simulated human gastrointestinal (GI) fluids. The assay enables biologically promising drug leads to be evaluated for solubility limitations earlier in the drug developmen...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21041
更新日期:2008-04-01 00:00:00
abstract::L-3-(3-Hydroxy-4-pivaloyloxyphenyl)alanine (1, NB-355) is a novel L-dopa prodrug. After oral administration with carbidopa in rats, 1 demonstrated 2.3 times longer duration (MRT) and 1.4 times larger bioavailability (AUC) on plasma L-dopa concentrations than those of L-dopa itself. Similar results were obtained in dog...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600780703
更新日期:1989-07-01 00:00:00