Ergotamine Tartrate, 1 Mg Rectally, is Biologically Active despite Unmeasurable Plasma Levels

Plasma levels and the vasoconstrictive effect of 1 mg ergotamine tartrate given as tablets or suppositories were compared. In a crossover study, eight male volunteers received tablets or suppositories containing ergotamine in a drug combination (Anervan®) and, as a control, suppositories without ergotamine. Blood sampling and measurement of toe-arm systolic gradients with a strain-gauge technique were done for up to 6 h and again after 24 h and 48 h. Only 29 of 160 blood samples contained detectable (>0.1 mg/ml) amounts of ergotamine, and kinetic comparison could not be performed. Only ergotamine-containing suppositories caused a significant ( p < 0.008) decrease in toe-arm systolic gradient which was significantly different ( p < 0.003) from the effects of ergotamine tablets and control suppositories. Rectal ergotamine is thus more biologically active, for the factor used, than oral ergotamine. We suggest that a rectal dose of 1 mg ergotamine tartrate should be tried as the initial dose in the treatment of migraine attacks.

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Bioavailability of naringenin chalcone in humans after ingestion of cherry tomatoes

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000574 ◽

2020 ◽

Vol 90 (5-6) ◽

pp. 411-416 ◽

Cited By ~ 2

Author(s):

Carina Kolot ◽

Ana Rodriguez-Mateos ◽

Rodrigo Feliciano ◽

Katharina Bottermann ◽

Wilhelm Stahl

Keyword(s):

Plasma Levels ◽

Average Concentration ◽

Biologically Active ◽

Thiol Groups ◽

Structural Element ◽

Active Molecule ◽

Reactive Center ◽

Average Maximum ◽

Alpha Beta ◽

Cherry Tomatoes

Abstract. Chalcones are a type of flavonoids characterized by an α-β unsaturated structural element which may react with thiol groups to activate pathways such as the Nrf2-Keap-1 system. Naringenin chalcone is abundant in the diet but little is known about its bioavailability. In this work, the bioavailability of naringenin chalcone from tomatoes was investigated in a group of healthy men (n=10). After ingestion of 600 grams of tomatoes providing a single dose of 17.3 mg naringenin chalcone, 0.2 mg of naringenin, and 195 mg naringin plasma levels of free and conjugated naringenin and naringenin chalcone (glucuronide and sulfate) were analyzed by UHPLC-QTOF-MS at 0.5, 1, 3, and 6 h post-consumption. Plasma levels of conjugated naringenin increased to about 12 nmol/L with a maximum at about 3 h. Concentrations of free naringenin hardly elevated above baseline. Plasma levels of free and conjugated naringenin chalcone significantly increased. A maximum of the conjugated chalcone was reached at about 3 h after ingestion with an average concentration of about 0.5 nmol/L. No free chalcone was detectable at baseline but low amounts of the unconjugated compound could be detected with an average maximum of 0.8 nmol/L at about 1 h after ingestion. The data demonstrate that naringenin chalcone is bioavailable in humans from cherry tomatoes as a dietary source. However, availability is poor and intramolecular cyclisation as well as extended metabolism likely contribute to the inactivation of the reactive alpha-beta unsaturated reactive center as well as the excretion of the biologically active molecule, respectively.

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Capillary Fragility Induced By Psychotropic Serotonergic Drugs

10.1055/s-0038-1651958 ◽

1981 ◽

Author(s):

D Shepro ◽

H B Hechtman

Keyword(s):

Psychotropic Drugs ◽

Plasma Levels ◽

Adrenergic Receptors ◽

Structural Integrity ◽

Single Injection ◽

Biologically Active ◽

Daily Injection ◽

Cutaneous Microcirculation ◽

5 Ht Uptake ◽

Serotonergic Drugs

In defining a mechanism for the putative platelet support of microvascular structural integrity, we have shown that serotonin (5-HT) injected into thrombocytopenic animals prevents petechial formation for as long as 6 h, and that psychomotor drugs inhibit this palliative action. Our data suggest that a platelet’s role is to deliver- release 5-HT into the cutaneous microcirculation in amounts physiologically above plasma levels, which acts as a signal to maintain “endothelial tone”. In this study psychotropic drugs known to inhibit 5-HT uptake, such as imipramine, amitriptyline, fluoxetine, were studied for their effect on endothelial structural integrity in normal adult hamsters. Adrenergic receptors, inhibitors and catecholamines were also used in conjunction with psychotropic drugs. Bleeding times and plasma levels of 5-HT were quantitated. Following a single injection or daily injection for 21 days of all substances tested, petechial sensitivity increased significantly in normal hamsters. Norepinephrine decreased and propanolol enhanced petechial formation. Microhemorrhages were observed within 5 min post-injection with fluoxetine (4.5 × 10-3 mg⋅100 g-1) and with amitriptyline (0.04 mg.100 g-1). Petechiae occurred for one week following a single injection of fluoxetine, which indicates that the stable metabolite of this antidepressant is biologically active. All other parameters measured were normal except bleeding times, which increased three-fold compared to controls. In published reports, 5-HT has been shown to alter microfilament orientation, especially at junctions. Based upon this observation and the present data, we theorize that the blockade of a 5-HT signal by the uptake antagonist effects endothelial cytoskeletal support of junctions.

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Correlation of plasma levels of free insulin-like growth factor 1 and clinical benefit of the IGF-IR inhibitor figitumumab (CP- 751, 871)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.3539 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 3539-3539

Author(s):

M. L. Hixon ◽

A. Gualberto ◽

L. Demers ◽

L. G. Paz-Ares ◽

S. Novello ◽

...

Keyword(s):

Growth Factor ◽

Plasma Levels ◽

Fold Increase ◽

Serum Markers ◽

Biologically Active ◽

Type I ◽

Insulin Like Growth Factor ◽

Survival Times ◽

Significant Treatment ◽

Treatment Naïve

3539 Background: Free IGF-1 (fIGF-1) represents the biologically active fraction of IGF-1, the main circulating ligand of the Insulin-like Growth Factor type I Receptor (IGF-IR). Signaling through the IGF-IR induces tumor survival and resistance to cancer therapy. Figitumumab (F) (CP-751,871) inhibits IGF-1-induced IGF-IR autophosphorylation with an IC50 of 0.42 nmol/L. Methods: Plasma levels of fIGF-1 were measured in a phase 1b/2 multi-center study of Paclitaxel (T) and Carboplatin (C) and F in patients (pts) with treatment-naïve NSCLC. Other serum markers of the IGF-IR pathway, including circulating soluble IGF-IR (sIGF-IR), IGFBP3 and ALS (acid-labile subunit), were also investigated. The Kaplan-Meier method was used to estimate median survival times. Results: A total of 536 blood samples from 159 pts were analyzed. Baseline median and range fIGF-1 were 0.53 and 0.07–1.99 ng/mL. fIGF-1 directly correlated with IGFBP3 and ALS, and inversely with sIGF-IR (Rho=-0.430, p=0.03). Treatment with F resulted in dose-dependent accumulation of fIGF-1 with a sustained >10 fold increase in fIGF-1 plasma levels at the 20 mg/kg dose, suggesting complete systemic blockade of fIGF-1 binding to the IGF-IR. sIGF-IR decreased and IGFBP3 increased in response to F, but increases in IGBP3 were more modest than those of fIGF-1. Baseline plasma levels of fIGF-1 had a 96.6% negative predictive value for PFS status at 6 months (p=0.03). Median PFS were respectively 2.73 and 6.53 months for TC alone and TC with F (20 mg/kg) in the high fIGF-1 group (p=0.001) while no significant treatment effect of F was observed in the low (<0.54 ng/mL) fIGF-1 group. Sixty three percent of pts with high fIGF-1 had tumors of adenocarcinoma histology. Conclusions: IGF-1 is a key element in the biology of NSCLC of adenocarcinoma histology and its determination may contribute to the identification of pts who benefit from figitumumab therapy. [Table: see text]

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EFFECTS OF SURGERY ON PLASMA LEVELS OF CORTISOL, CORTICOSTERONE AND NON-PROTEIN-BOUND-CORTISOL

Acta Endocrinologica ◽

10.1530/acta.0.0640439 ◽

1970 ◽

Vol 64 (3) ◽

pp. 439-451 ◽

Cited By ~ 23

Author(s):

Yuji Hamanaka ◽

Hisao Manabe ◽

Hideyuki Tanaka ◽

Yasumasa Monden ◽

Tohru Uozumi ◽

...

Keyword(s):

Diurnal Variation ◽

Plasma Levels ◽

Plasma Cortisol ◽

Equilibrium Dialysis ◽

Chronically Ill ◽

Biologically Active ◽

Major Surgery ◽

Corticosterone Concentration ◽

Control Subjects ◽

Maximum Value

ABSTRACT The diurnal variation in plasma cortisol, corticosterone and non-protein-bound cortisol was investigated using altogether 991 plasma samples obtained from preoperative chronically ill (control) subjects and patients during and following major surgery. A fluorimetric method using an elution chromatography on Amberlite IRC-50 and the equilibrium dialysis method were used for the determinations. The diurnal variation in plasma cortisol of the preoperative control subjects reached a peak (17.3 μg/100 ml) at 6 a.m. and declined to the lowest level (2.3 μg/100 ml) between 10 p.m. and midnight. The maximum value in the levels of corticosterone (0.6 μg/100 ml) was observed at 6 a.m. Surgery caused a steep rise in plasma cortisol showing a maximum value (30.0 μg/100 ml) 2 to 4 hours after the end of the operation. Although the average of the morning levels of plasma cortisol returned to the control levels within 4 to 5 days, the evening levels returned on the 6th day after the operation. The response of plasma corticosterone in the surgery group was found to parallel the change in plasma cortisol. However, the increase in the corticosterone concentration was significantly higher than that of cortisol. The percentage of non-protein-bound cortisol in the plasma of the preoperative control subjects was found to be 2.5 to 3.3 per cent at 6 and 8 a.m. and 1.5 per cent at midnight, while the percentage remained almost unchanged (about 2%) at 10 a.m., 12 a.m. and 6 p.m. The percentage increased significantly during and for 4 days following the operation, concomitant with the increase in the levels of plasma cortisol. It is suggested that stressful situations are associated with markedly increased plasma levels of biologically active cortisol.

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Decreased circulating levels of active ghrelin are associated with increased oxidative stress in obese subjects

Acta Endocrinologica ◽

10.1530/eje.1.01977 ◽

2005 ◽

Vol 153 (3) ◽

pp. 403-407 ◽

Cited By ~ 34

Author(s):

Mina Suematsu ◽

Akira Katsuki ◽

Yasuhiro Sumida ◽

Esteban C Gabazza ◽

Shuichi Murashima ◽

...

Keyword(s):

Oxidative Stress ◽

Plasma Levels ◽

Active Form ◽

Inverse Correlation ◽

Normal Subjects ◽

Biologically Active ◽

Prostaglandin F ◽

Obese Subjects ◽

Circulating Levels ◽

And Oxidative Stress

Objective: To investigate the relationship between active ghrelin and oxidative stress in obese subjects. Design: We measured the plasma levels of free 8-epi-prostaglandin F2α (8-epi-PGF2α, a reliable and systemic marker of oxidative stress) and the active form of ghrelin in 17 obese and 17 normal subjects. The biologically active forms of ghrelin were measured using a commercially available radio-immunoassay kit and free 8-epi-PGF2α was measured using an enzyme immunoassay kit. Results: The circulating level of active ghrelin was significantly decreased (20.4 ± 2.6 vs 40.9 ± 3.9 fmol/ml, P < 0.01) while that of 8-epi-PGF2α was significantly increased (61.5 ± 9.6 vs 17.3 ± 3.4 pg/ml, P < 0.01) in obese subjects compared with normal subjects. The plasma levels of active ghrelin and 8-epi-PGF2α were significantly correlated in obese (r = −0.507, P < 0.05) and in all (r = −0.577, P < 0.01) subjects. Multivariate analysis showed that the plasma levels of active ghrelin and 8-epi-PGF2α were significantly and independently correlated in all subjects (F = 7.888, P < 0.01). Conclusions: There is an inverse correlation between circulating levels of active ghrelin and oxidative stress in obesity. Low circulating levels of active ghrelin may enhance oxidative stress and the process of atherosclerosis in obese subjects.

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Cyclophosphamide pharmacokinetics: correlation with cardiac toxicity and tumor response.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.6.995 ◽

1992 ◽

Vol 10 (6) ◽

pp. 995-1000 ◽

Cited By ~ 114

Author(s):

L J Ayash ◽

J E Wright ◽

O Tretyakov ◽

R Gonin ◽

A Elias ◽

...

Keyword(s):

Plasma Levels ◽

Tumor Response ◽

Parent Compound ◽

Autologous Bone Marrow Transplantation ◽

Metastatic Breast ◽

Subsequent Development ◽

Biologically Active ◽

Pharmacokinetic Data ◽

Active Metabolites ◽

Metastatic Breast Carcinoma

BACKGROUND Cyclophosphamide, which forms the nucleus for virtually all preparative regimens for autologous bone marrow transplantation (ABMT), is an alkylating agent of which cytotoxicity is not directly caused by the parent compound but by its biologically active metabolites. Its nonmyelosuppressive toxicity in the ABMT setting is cardiomyopathy. We attempted to determine any correlation between plasma levels of total cyclophosphamide and the subsequent development of cardiac dysfunction. PATIENTS AND METHODS Analyses of plasma levels and the derivation of plasma concentration-time curves (area under the curve [AUC]) were performed in 19 women with metastatic breast carcinoma, who received a continuous 96-hour infusion of cyclophosphamide, thiotepa, and carboplatin (CTCb) with ABMT. The assay for total cyclophosphamide measures the inactive parent compound; reliable assays of the active metabolites of cyclophosphamide are not yet available. RESULTS Six of 19 women developed moderate, but transient, congestive heart failure (CHF) as assessed by clinical and radiologic criteria. These patients had a significantly lower AUC of total cyclophosphamide (median, 2,888 mumol/L/h) than patients who did not develop CHF (median, 6,121 mumol/L/h) (P less than .002). Median duration of tumor response in these patients was also more durable; at least 22 months in patients with lower AUCs versus a median of 5.25 months in those with higher AUCs (P = .008). CONCLUSION These pharmacokinetic data support the premise that enhancement of cyclophosphamide activation may lead to both greater tumor cytotoxicity and increased but reversible end-organ toxicity. Early analysis of pharmacokinetic data may allow modulation of cyclophosphamide administration in an attempt to enhance therapeutic efficacy.

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The diagnostic and prognostic value of mature and total adrenomedullin for sepsis: a prospective, observational study

10.21203/rs.2.19873/v2 ◽

2021 ◽

Author(s):

Tetsu Yonaha ◽

Toyoaki Maruta ◽

Go Otao ◽

Koji Igarashi ◽

Sayaka Nagata ◽

...

Keyword(s):

Plasma Levels ◽

Prospective Observational Study ◽

Operating Characteristic ◽

Final Analysis ◽

Biologically Active ◽

Sepsis Group ◽

Receiver Operating Characteristic Curves ◽

Single Centre Study ◽

Sepsis And Septic Shock ◽

Diagnostic And Prognostic Value

Abstract Background: Biologically active adrenomedullin (mature AM) has received considerable attention as a new biomarker of sepsis and septic shock. However, information about this peptide is limited. In this study, we further investigated the value of mature AM for diagnosis and outcome prediction in sepsis.Methods: This was a prospective, observational, single-centre study. Patients admitted to the intensive care unit (ICU) were retrospectively categorised into non-sepsis or sepsis groups, according to the Sepsis-3 definitions. Plasma levels of mature and total (the sum of the levels of intermediate and mature forms) AM were measured, and their usefulness was compared with those of other sepsis biomarkers, such as procalcitonin and presepsin. Results: Of the 98 patients included in the final analysis, 42 were assigned to the non-sepsis and 56 to the sepsis group. Levels of mature and total AM on admission were significantly higher in patients with sepsis than in those without sepsis. The areas under the receiver operating characteristic curves of mature and total AM for predicting 28-day mortality in patients with sepsis became significant on day 3 after admission. A good correlation between the AM forms was found, indicating that the changes in their plasma levels may directly reflect each other.Conclusion: Because the levels of mature and total AM increased significantly in patients with sepsis on admission, both forms may be used as reliable and early biomarkers for diagnosing sepsis according to the Sepsis-3 definitions. However, prediction of 28-day mortality in such patients would require several days of ICU stay.

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Ergotamine Abuse: Results of Ergotamine Discontinuation, With Special Reference To the Plasma Concentrations

Cephalalgia ◽

10.1046/j.1468-2982.1982.0204189.x ◽

1982 ◽

Vol 2 (4) ◽

pp. 189-195 ◽

Cited By ~ 36

Author(s):

Veli Ala-Hurula ◽

Vilho Myllylä ◽

Eero Hokkanen

Keyword(s):

Drug Abuse ◽

Detection Limit ◽

Side Effects ◽

Special Reference ◽

Plasma Levels ◽

Plasma Concentrations ◽

Withdrawal Symptoms ◽

Daily Dose ◽

Ergotamine Tartrate

Twenty-three patients suffering from continuous headache linked with habitual daily use of ergotamine tartrate were studied. Their headaches were classified clinically, and possible side effects of ergotamine medication, plasma levels of ergotamine, and occurrence of withdrawal symptoms after discontinuation of drug abuse were recorded. Seventeen of the patients were clinically diagnosed as suffering from “ergotamine headache”, and seven of them complained of coldness in the extremities. Plasma ergotamine levels were measured by using a radioimmunoassay. In almost half of the patients the 1 h plasma levels after the daily dose were below the detection limit of the procedure (0.12 ng/ml). The duration and severity of the withdrawal symptoms did not correlate with the doses and plasma levels of ergotamine. In only 4 of the 21 patients who were followed up for 3 to 6 months did headache symptoms not improve after ergotamine withdrawal. The results indicate that even small (0.5-1.0 mg/day) doses of ergotamine tartrate taken regularly may cause continuous headache symptoms and withdrawal symptoms after discontinuation.

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LUTEINIZING HORMONE LEVELS DURING THE MENSTRUAL CYCLE OF THE BABOON (PAPIO HAMADRYAS)

Acta Endocrinologica ◽

10.1530/acta.0.0910049 ◽

1979 ◽

Vol 91 (1) ◽

pp. 49-58 ◽

Cited By ~ 10

Author(s):

N. Goncharov ◽

A. V. Antonichev ◽

V. M. Gorluschkin ◽

L. Chachundocova ◽

D. M. Robertson ◽

...

Keyword(s):

Menstrual Cycle ◽

Luteinizing Hormone ◽

Plasma Levels ◽

Luteal Phase ◽

Follicular Phase ◽

Papio Hamadryas ◽

Biologically Active ◽

Plasma Progesterone ◽

Lh Surge

ABSTRACT The peripheral plasma levels of luteinizing hormone (LH) as measured by an in vitro bioassay method were determined in daily plasma samples collected throughout one menstrual cycle in 8 normally menstruating baboons (Papio hamadryas). In addition LH was measured in plasma at three hourly intervals throughout the day in the follicular, peri-ovulatory and luteal phases of the cycle in 7, 3 and 6 animals respectively. The plasma levels of progesterone and oestradiol were also determined in the same samples throughout the menstrual cycle and during the period of the midcycle LH surge. The circulating LH profile measured throughout the cycle was characterized by a sharp mid-cycle surge (completed within one day) which was followed by a series of LH surges of varying intensity during the luteal phase of the cycle. The initial surge was considered to be pre-ovulatory as indicated by its relationship to the peak of plasma oestradiol and to the first significant increase in the levels of plasma progesterone above values found earlier in the follicular phase. A circadian rhythm of LH was observed during the luteal phase of the cycle; a 3 fold rise in LH was noted during the hours 15.00 to 24.00. No differences were observed throughout the day in the follicular phase of the cycle. The LH profile in three animals studied during the mid-cycle LH surge showed pronounced circadian changes with a major peak at 24.00 h. Plasma progesterone levels during this period rose sharply to values normally found in the mid-luteal phase of the cycle. A comparison of plasma levels of biologically active LH during the menstrual cycle of the baboon with those found in normally menstruating women reveals that in the baboon the LH peak is of much shorter duration and the levels in the follicular and peri-menstrual phases are significantly lower than in the human.

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