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Biomedical subjects

J T Biggs

Publications and source records attributed to J T Biggs.

86 records · Page 5Linked to original sources
PubMed1975

Tricyclic antidepressant overdose: clinical presentation and plasma levels.

Fifteen patients were studied at 8- to 12-hr intervals during the first 24 hr after overdosing with tricyclic antidepressants, and subsequently followed daily for up to 144 hr. The severity of the overdose was determined by measuring the plasma tricyclic antidepressant level using gas chromatography-mass fragmentography. No correlation was found between total, tertiary, or desmethyl tricyclic antidepressant plasma levels and maximum heart rate, lowest blood pressure, degree of unconsciousness, or EKG changes involving the P-R interval or ST-T wave changes. There was a weak correlation between drug plasma level and maximum pupil size (r = 0.46; p less than 0.05) and a strong correlation between the duration of the QRS complex and tricyclic antidepressant plasma levels (r = 0.75; p less than 0.01). All patients with a total tricyclic antidepressant plasma level greater than or equal to 1,000 ng/ml had a QRS interval greater than or equal to 100 msec. As the total plasma tricyclic level fell, the duration of the QRS interval returned to normal. Thus, the duration of the QRS complex on the electrocardiogram appears to be the most reliable clinical sign for evaluating the seriousness of tricyclic antidepressant overdosage.

Adolescent↗
PubMed1975

Renal and biliary disposition of dapsone in the dog.

Dapsone (4,4'-diaminodiphenylsulfone [DDS]) was administered intravenously to anesthetized dogs; urine was collected, heparinized venous blood was obtained, and bile was collected from some of the dogs. A constant infusion of inulin was maintained, and isosmotic or hypoosmotic fluids were administered. Dogs were studied under conditions of standardized, increased or decreased urine flow, and before and after plasmapheresis. Plasma, urine, and bile samples were analyzed for DDS and DDS conjugates; the degree of binding of DDS by plasma proteins was also determined. The renal clearances of inulin and DDS were calculated. No monoacetyldapsone (MADDS) was detected in the plasma, and only negligible quantities were found in the urine. Small quantities of DDS and DDS conjugates were detected in the bile in 4 h following the dose. Between 10 and 30% of the administered drug could be identified as DDS plus DDS conjugates in the urine in 8 h after the dose. Renal clearance of unbound DDS was proportional to the urine flow rate, and the clearance ratio of DDS to inulin approached the same maximal value as that for urea. Although the rate of urinary excretion of DDS conjugates was the same in the dog as in man, the rates of excretion of DDS and of DDS plus DDS conjugates were greater in the dog than in man, suggesting that the acetylation of DDS to MADDS by man but not by the dog and the greater degree of plasma protein binding of DDS and MADDS by man account for the longer half-time of disappearance of DDS in man compared to that in the dog.

Animals↗
PubMed1975

Steady-state protriptyline levels in an outpatient population.

The authors measured steady-state protriptylive levels in 12 outpatients undergoing treatment for depression. The steady-state level of protriptyline was surprisingly high compared with levels obtained when other tricyclic antidepressants were prescribed. This finding probably accounts for the effectiveness of protriptyline at low doses and its frequent side effects.

Administration, Oral↗
PubMed1975

The disposition of dapsone and monoacetyldapsone in the dog (38516).

Four female dogs receiving 1.0 mg dapsone (DDS)/kg iv exhibited logarithmic decline of plasma levels of DDS with a mean half-time of disappearance (T-1/2 of 11.7 hr. No evidence of acetylation of DDS to monoacetyl DDS (MADDS) was found. An equimolar dose of MADDS was deacetylated slowly to DDS by the same dogs. The mean T 1/2 of MADDS was 6.5 hr, significantly less than that of DDS. In 2-hr plasma samples after these doses of drugs, protein-binding of DDS and MADDS averaged 71 and 84%, respectively. Tests of protein-binding of the two drugs in vitro confirmed the observations in vivo.

Acetylation↗
PubMed1975

Disposition of dapsone and monoacetyldapsone in rats.

Female Buffalo and Lewis rats receiving 1.0 mg DDS/kg ip exhibited higher plasma levels of DDS and its monoacetylated metabolite, MADDS, than did male rats of each strain receiving the same dose. The fraction of the total measured drug in plasma as MADDS at 8 hr in female rats of both strains ranged from 43 to 62% compared with a range of 28-31% in male rats. Plasma half times of disappearance (T1/2) of DDS ranged from 5.0 to 6.8 hr and were not different among sexes and strains. Deacetylation of MADDS to DDS occurred when equimolar doses of MADDS were administered. An approach to a steady state of acetylation-deacetylation was indicated by comparing the percentage MADDS of the total drug in plasma in the respective sexes and strains receiving both drugs. T1/2 values of MADDS were significantly lower than values for DDS in Lewis rats. They were not different in Buffalo rats. Protein binding studies in plasma from rats receiving 5.0 mg DDS or 5.8 mg MADDS/kg showed 67-72% binding of DDS and 91% binding of MADDS. These in vivo observations were confirmed by in vitro binding studies. Comparison of these results with those of earlier studies in mice and man indicates that the rat is a better model of man than is the mouse for studies on the disposition of DDS.

Animals↗