Quantitative determination of guanethidine and other guanido-containing drugs in biological fluids by gas chromatography with flame ionization detection and multiple ion detection

Jh, Hengstmann; Fc, Falkner; Jt, Watson; Oates, J A

doi:10.1021/ac60337a045

Cited by 44 publications

(7 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3 Guaneptidine, an analogue of guanethidine with a 7-membered ring as the only structural difference between the two substances, was used as the internal standard because of its physico- l l Hand pressure was measured through a 21-gauge scalp needle inserted into a superficial vein on the dorsum of the hand, and connected to a Hewlett-Packard pressure transducer (Model 1280) with the tip of the needle as the reference point.…”

Section: Methodsmentioning

confidence: 99%

“…Blood pressure alone is not always a helpful parameter in deciding when the sympathetic nervous system is blocked. 3 This assay makes it possible to measure guanethidine plasma levels in patients receiving the drug for therapy of hypertension. 2 Therefore, the hemodynamic response to Valsalva's maneuver has been used as a more reliable indicator of the integrity of the sympathetic nervous system, since guanethidine does abolish the post-Valsalva blood pressure overshoot and bradycardia.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Relationship of Plasma Guanethidine Levels to Adrenergic Blockade

et al. 1977

View full text Add to dashboard Cite

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

The Relationship of Plasma Guanethidine Levels to Adrenergic Blockade

et al. 1977

View full text Add to dashboard Cite

“…Previous studies have shown that inter-individual differences in response to the hypotensive adrenergic blocking drug debrisoquine are due to individual variations in the rates of metabolism of the drug (Angelo, Dring, Lancaster, Latham & Smith, 1975;Angelo, Dring, Lancaster & Smith, 1976 For absorption studies, ten subjects received bethanidine (30 mg orally) and the amount of unchanged drug excreted in the 24 h urine was analysed by g.l.c. using an adaption of the method described by Hengstmann, Falkner, Watson & Oates (1974). The amount of unchanged bethanidine recovered in the…”

mentioning

confidence: 99%

“…For absorption studies, ten subjects received bethanidine (30 mg orally) and the amount of unchanged drug excreted in the 24 h urine was analysed by g.l.c. using an adaption of the method described by Hengstmann, Falkner, Watson & Oates (1974). The amount of unchanged bethanidine recovered in the urine ranged from 48-79% of the dose (62.3 + 9.9%: mean + s.d.)…”

mentioning

confidence: 99%

Absence of correlation between the oral pharmacokinetics and response to bethanidine [proceedings]

Dring¹,

Kamanyiro²,

Lancaster³

et al. 1977

Brit J Clinical Pharma

View full text Add to dashboard Cite

maintenance of blood pressure. We report the effect of noradrenaline infusion on blood pressure and plasma noradrenaline concentration following oral administration ofclonidine (300 tg) to four normal subjects.Intravenous cannulae were inserted into each anticubital fossae; a 3 in catheter on the left and a 12 in catheter on the right. Blood pressure was measured using a Roche Arteriosonde 1217 with the pressure cuff on the right arm. Blood for plasma noradrenaline measurements was drawn from the left arm and noradrenaline was infused through the right arm cannula. Noradrenaline infusion was started 4 h after clonidine administration and the rate of infusion was increased in a stepwise fashion. Rates of 0.01, 0.03, 0.05, 0.075, 0.10 and 0.200 tg kg-' min-' were used and infusion at each rate was continued for 10 min. Noradrenaline administration was stopped when the systolic blood pressure reached a value 30% greater than the pre-dose value. Pulse rate was measured continuously, blood pressure was measured every 2 min during the noradrenaline infusion and blood for noradrenaline was withdrawn before clonidine, 4 h after clonidine and at the eighth and tenth min of each infusion.The 1.44+0.54ng/ml in the four subjects. There were marked differences between subjects in the plasma noradrenaline levels achieved at any given infusion rate; at 0.10 tg kg-' min-' the mean value was 2.62 + 0.72 with a range of from 0.85 ng/ml to 4.35ng/ml. The sensitivity of blood pressure to changes in plasma noradrenaline also varied markedly between subjects. These results show that restoration of the concentration of noradrenaline in plasma to control levels does not reverse the hypotensive effect of clonidine. Following oral or intravenous administration of this agent, circulating noradrenaline does not appear to be responsible for the delayed fall in blood pressure. Previous studies have shown that inter-individual differences in response to the hypotensive adrenergic blocking drug debrisoquine are due to individual variations in the rates of metabolism of the drug (Angelo, Dring, Lancaster, Latham & Smith, 1975;Angelo, Dring, Lancaster & Smith, 1976 For absorption studies, ten subjects received bethanidine (30 mg orally) and the amount of unchanged drug excreted in the 24 h urine was analysed by g.l.c. using an adaption of the method described by Hengstmann, Falkner, Watson & Oates (1974). The amount of unchanged bethanidine recovered in the

show abstract

“…We have recently described a highly sensitive assay for the detection of guanethidine in plasma in the ng/ ml range. 3 This assay makes it possible to measure guanethidine plasma levels in patients receiving the drug for therapy of hypertension. The purpose of the investigation reported here was to investigate the relationship of plasma levels measured during chronic therapy to adrenergic blockade.…”

mentioning

confidence: 99%

The relationship of plasma guanethidine levels to adrenergic blockade

Walter

Khandelwal

Falkner

et al. 1975

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Seventeen hypertensive patients receiving guanethidine for therapy were studied to determine the relationship of guanethidine plasma levels to adrenergic blockade. Plasma levels of guanethidine were measured by gas chromatography-mass spectrometry, and adrenergic blockade was defined by determining the venous reflex response to Valsalva maneuver or deep breath. A significant correlation was found between the change in the venous reflex response and the fall in mean standing pressure when guanethidine is given to patients maintained on a sodium restricted diet. A linear relationship was found between dose and plasma guanethidine concentration (p < 0.0001), but there was a 6jold interindividual variation in the plasma levels resulting from any given dose. Adrenergic blockade occurred when plasma levels were 8 nglml or higher. These results indicate that the large individual variation in dose requirements for the hypotensive effects of guanethidine most likely is not due to requirements for greatly different plasma levels of the drug; that the variation must result from pharmacokinetic determinants of differing plasma levels between individuals or from other factors, such as increased plasma volume, which maintain elevated arterial pressure in the face of adrenergic blockade.The relationship between the dose of guanethidine and the hypotensive response in the population of patients with hypertension is not predictable. Possible explanations for this variability include individual differences in sensitivity of the adrenergic nervous system to the drug and individual pharmacokinetic dif-

show abstract

Quantitative determination of guanethidine and other guanido-containing drugs in biological fluids by gas chromatography with flame ionization detection and multiple ion detection

Cited by 44 publications

References 7 publications

The Relationship of Plasma Guanethidine Levels to Adrenergic Blockade

The Relationship of Plasma Guanethidine Levels to Adrenergic Blockade

Absence of correlation between the oral pharmacokinetics and response to bethanidine [proceedings]

The relationship of plasma guanethidine levels to adrenergic blockade

Contact Info

Product

Resources

About