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  • 1
    Electronic Resource
    Electronic Resource
    The Influence of Regional Deposition on the Pharmacokinetics of Pulmonary-Delivered Human Growth Hormone in Rabbits (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 356-359 
    Details
    ISSN: 1573-904X
    Keywords: growth hormone ; pulmonary ; pharmacokinetics ; gamma scintigraphy ; drug delivery ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pulmonary deposition and pharmacokinetics of human growth hormone (hGH), administered by aerosol and instillate, in formulations containing 99mTc-DTPA (for gamma scintigraphic imaging) have been studied in five male New Zealand White rabbits. Gamma scintigraphy indicated that the peripheral:central deposition tended to be greater for aerosol (1.54) than for instillate (0.8). Two gamma scintigraphic methods were used to quantify dose deposited by aerosol, which permitted bioavailabilities to be determined. The bioavailable fraction for aerosolized hGH (45%) was greater than for instilled hGH (16%). This was attributed to the differential effects of mucociliary clearance. Absorption rate limited pharmacokinetics prevailed for both hGH formulations with post-peak half-lives approximately 10-fold greater than the intravenous elimination half-life of 40 min. Apparent absorption rate constants resulting from instillation and aerosolization were equivalent (0.0012 min−1and 0.0020 min−1respectively), however lung-to-blood transfer rate constants for aerosol delivery (0.00071 min −l) were greater than for instillation (0.00018 min−1).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016292232513
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Pulmonary First-Pass and Steady-State Metabolism of Phenols (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 744-748 
    Details
    ISSN: 1573-904X
    Keywords: phenol ; 1-naphthol ; UDPGT ; pulmonary ; first-pass ; steady-state extraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To study (A) the effect of the administration route (i.v. and i.t.) on pre- and post-absorptive metabolism of phenol and 1-naphthol by the lung and (B) pulmonary extraction of phenol at steady-state. Methods. Phenols were administered intra-arterially, intravenously and intratracheally and the pre- and post-absorptive metabolism assessed by comparing the AUCs in arterial blood. Phenol was infused to steady-state and the pulmonary extraction assessed by measuring jugular vein and carotid artery blood concentrations. Results. In contrast to previously published data (e.g., Mistry and Houston, Drug Metab. Dispos. 13:740–745 (1985)) we could not detect pulmonary first-pass metabolism of the phenols; reasons for this disparity are discussed. An apparent negative pulmonary extraction of phenol at steady-state was observed, probably as a consequence of extraction by organs which are in series, and not parallel, with the lungs (e.g. liver, kidneys and GIT). Conclusions. (A) Phenol and 1-naphthol do not undergo pulmonary first-pass metabolism. (B) Traditional methods of assessing organ extraction and clearance at steady-state cannot be utilised when metabolising organs are in series.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016003717666
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    The Influence of Liposomal Encapsulation on Sodium Cromoglycate Pharmacokinetics in Man (1989)
    Springer
    Pharmaceutical research 6 (1989), S. 633-636 
    Details
    ISSN: 1573-904X
    Keywords: sodium cromoglycate ; liposome ; liposomal ; drug delivery system ; pulmonary drug delivery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of pulmonary-administered sodium cromoglycate (SCG) has been studied in five healthy volunteers. SCG, 20 mg, was inhaled as a solution and encapsulated in dipalmitoyl phosphatidylcholine/cholesterol (1:1) liposomes. Liposomal SCG produced detectable drug levels in plasma from four volunteers taken 24 and 25 hr after inhalation. Inhaled SCG solution, although producing peak plasma levels more than sevenfold greater than liposomal drug, was not detectable in 24-hr samples from any volunteer. The decline in plasma levels following inhalation of liposomal SCG (reflecting the absorption phase) was best described by a biexponential equation. The two absorption rate constants differed by more than an order of magnitude. The rapid absorption phase was probably due to free or surface-adsorbed SCG in the liposomal formulation, since the absorption rate constant for this phase did not differ significantly from the absorption rate constant for SCG in solution. The phase of slow drug absorption may then be attributed to absorption of drug released from vesicles. The data indicate that encapsulation of SCG prior to pulmonary administration prolonged drug retention within the lungs and altered its pharmacokinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015917918130
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Differential Effects of Anesthetic Regimens on Gentamicin Pharmacokinetics in the Rat: A Comparison with Chronically Catheterized Conscious Animals (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 41-45 
    Details
    ISSN: 1573-904X
    Keywords: gentamicin ; carboxyinulin ; pharmacokinetics ; anesthesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The intravenous disposition of gentamicin was compared in the conscious chronically catheterized rat with that in rats anesthetized using five injectable laboratory anesthetics. Gentamicin plasma clearance in the conscious rat was significantly higher than in animals anesthetized with urethane, fentanyl/ fluanisone/midazolam, pentobarbitone, or ketamine/midazolam but similar to that in rats anesthetized with alphaxolone/alphadolone. Urethane anaesthesia resulted in a significantly lower gentamicin clearance than in all other groups. Gentamicin clearance in rats anesthetized with alphaxolone/alphadolone was significantly higher than in rats anesthetized with either fentanyl/fluanisone/midazolam or urethane. No significant differences in the volume of distribution of gentamicin were observed between any of the groups studied, either anesthetized or conscious. Carboxyinulin blood clearance in the conscious group was significantly higher than that with urethane, fentanyl/fluanisone/midazolam, pentobarbitone, or ketamine/midazolam but not significantly different from alphaxolone/ alphadolone-anesthetized animals. The differences in carboxyinulin clearance were noted to be proportional to the differences in gentamicin clearance (r 2 = 0.98). These results demonstrate that the choice of anesthetic used in laboratory pharmacokinetic studies is important. Gentamicin clearance was higher in conscious than anesthetized rats, and it may be prudent to use chronically catheterized animals in pharmacokinetic studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015879324354
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    The Pharmacokinetics of Pulmonary-Delivered Insulin: A Comparison of Intratracheal and Aerosol Administration to the Rabbit (1992)
    Springer
    Pharmaceutical research 9 (1992), S. 764-768 
    Details
    ISSN: 1573-904X
    Keywords: insulin ; aerosol ; pulmonary ; pharmacokinetics ; gamma scintigraphy ; drug delivery ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pulmonary deposition and pharmacokinetics of insulin, administered via an endotracheal tube as an aerosol and instillate, in formulations containing either 113mIn-DTPA or 99mTc-DTPA (for gamma scintigraphic imaging) have been studied in four male New Zealand White rabbits. Using a randomized crossover design, the pharmacokinetics of intravenous insulin were also characterized. Recovery of immunoreactive insulin after nebulization was greater than 90%, indicating that the aerosolisation procedure did not cause appreciable insulin degradation. Gamma scintigraphy demonstrated that the penetration index (peripheral:central deposition) for the aerosolized formulation (1.52) was much greater than that for the instillate (0.32). Gamma scintigraphy also allowed exact quantification of the dose deposited after aerosol administration and thus permitted accurate determination of bioavailabilities. The bioavailable fraction for aerosolized insulin was 10-fold greater than for instilled insulin (57.2 vs 5.6%). Mucociliary clearance was likely to be greater for the instillate since it showed a preferential central deposition; this may account for the lower bioavailability. Insulin pharmacokinetics from both pulmonary formulations were absorption rate limited, resulting in postpeak half-lives which were approximately 20-fold greater than the intravenous elimination half-life (3 min). The apparent absorption rate constants resulting from instillation and aerosolisation were statistically equivalent (0.015 and 0.011 min−1, respectively). Mucociliary clearance of insulin would result in an overestimation of the true absorption rate constant; hence if mucociliary transport were greater for the instillate, then the true airways to blood transfer rate constant will be higher for the aerosolized formulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015851521551
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    Paper (German National Licenses)
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