Administered peptides inhibit the degradation of endogenous peptides. The dilemma of distinguishing direct from indirect effects

LaBella, Frank S.; Geiger, Jonathan D.; Glavin, Gary B.

doi:10.1016/0196-9781(85)90168-8

Cited by 34 publications

(14 citation statements)

References 228 publications

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“…The negative correlations between BENDI levels in CSF and those in the NTS area may indicate that BEND has been released in the NTS area. Released BEND is usually broken down by peptidases [45], and the increase in CSF peptides may be due to immature peptidases or by their inhibition by other peptides [24]. If insufficient peptide breakdown is combined with increased activity in the BEND-ACTH axis, a steady increase in BEND may reach levels that cause respiratory depression, bradycardia and hypotension [1,17,38].…”

Section: Discussionmentioning

confidence: 99%

Inverse relationship between beta-endorphin immunoreactivity in cerebrospinal fluid and nucleus tractus solitarius in sudden infant death

Storm

Rognum²,

Reichelt

1994

Eur J Pediatr

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In nucleus tractus solitarius (NTS) beta-endorphin (BEND) induces bradycardia and respiratory depression which have been reported to precede death in sudden infant death (SID). Of SID victims, 50% have elevated levels of beta-endorphin immunoreactivity (BENDI) in the cerebrospinal fluid (CSF), and 50% had undetectable levels. We therefore investigated the relationship of BENDI in the CSF to BENDI levels in the NTS area. This study included SID victims (CSF from n = 47, brain stem from n = 16), borderline SID victims (CSF and brain stem from n = 2), sudden death in childhood (CSF and brain stem from n = 1), and controls (CSF from n = 32, brain stem from n = 11). BEND in CSF and NTS area, after extraction, was measured by radioimmunoassay. High performance liquid chromatography was used for closer identification of BENDI. We found that the SID victims divided into two subpopulations, one having a relatively high BENDI level in CSF and one having no detectable level (P < 0.01). Furthermore, an inverse relationship was found between BENDI level in CSF and BENDI level in NTS area in the SID victims (P < 0.05). We conclude that increased BENDI level in CSF is associated with low BENDI level in the NTS area in 50% of SID victims. The low BENDI level in the NTS area may be due to increased release of BEND.

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Section: Discussionmentioning

confidence: 99%

Inverse relationship between beta-endorphin immunoreactivity in cerebrospinal fluid and nucleus tractus solitarius in sudden infant death

Storm

Rognum²,

Reichelt

1994

Eur J Pediatr

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“…In addition to metabolites, the presence of any endogenous substance can also have a profound effect on analytical results if they exist in high quantities. This is often the case for peptides; a good review of this consideration for peptides is provided by LaBella et al (1985). The presence of antibodies may interfere with the assay of the molecule of interest and, similarly, the molecule of interest may interfere with the antibody assay.…”

Section: Assay Interferencementioning

confidence: 98%

“…Endogenous effects must be controlled for in elucidating mechanisms and in distinguishing the effects of exogenously administered drug. A good review of this dilemma with respect to peptides is available (laBella et al 1985). Control of endogenous interference is equally true for delineation of accurate pharmacokinetics of exogenously administered peptides and proteins.…”

Section: Endogenous Interferencementioning

confidence: 99%

The Role of Pharmacokinetics in the Development of Biotechnologically Derived Agents

Wills¹,

Ferraiolo²

1992

Clinical Pharmacokinetics

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“…As we will'see later, endogenous binding proteins play an important role in the modulation of the biological activity and pharmacokinetics of certain macromolecular substances. By the very nature of their affinity and specificity for these mac~omolecules, the potential impact of these binding proteins upon immunoassay methods designed to quantify these macromolecules may be significant (19,20) due to them competing with the immunoassay antibody for the antigen (the molecule being quantified). In vivo antibody formation in response to administration of a foreign therapeutic protein may impact immunoassay methodology in the same way as endogenous binding proteins.…”

Section: Bioanalysismentioning

confidence: 99%

The relevance of pharmacokinetics in the development of biotechnology products

Toon

1996

European Journal of Drug Metabolism and Pharmacokinetics

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Biotechnology derived medicines will have an increasing impact not only upon medical practice but also upon the working lives of many pharmaceutical scientists. Whilst such medicines may be viewed as highly sophisticated to the clinician and scientist, the computer will still rightly demand that they are both efficacious and safe. Impacting as it does upon all phases of drug development and facilitating quantitative relationship between administered dose and systemic drug concentration, pharmacokinetics has an important role to play in the development of all medicines. Bioanalysis is an essential prelude to any pharmacokinetic investigation. For many biotechnology products the immunoassay and bioassay methodologies employed are often relatively non-specific and imprecise and yield assay dependent pharmacokinetic parameters. Other factors may also confound the pharmacokinetic evaluation of biotechnological products. In vivo binding proteins (including antibodies) may not only interfere with bioanalytical methodology but also have a significant effect on the pharmacokinetics and biological activity of certain macromolecules. Antibody formation is a particular problem in the preclinical evaluation of human proteins. Unlike most conventional pharmaceuticals, the rate and time of delivery into the systemic circulation is a fundamental component of the biological activity of many biological molecules.

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Administered peptides inhibit the degradation of endogenous peptides. The dilemma of distinguishing direct from indirect effects

Cited by 34 publications

References 228 publications

Inverse relationship between beta-endorphin immunoreactivity in cerebrospinal fluid and nucleus tractus solitarius in sudden infant death

Inverse relationship between beta-endorphin immunoreactivity in cerebrospinal fluid and nucleus tractus solitarius in sudden infant death

The Role of Pharmacokinetics in the Development of Biotechnologically Derived Agents

The relevance of pharmacokinetics in the development of biotechnology products

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