Concept of a Volume of Distribution and Possible Errors in Evaluation of This Parameter

Riegelman, Sidney; Loo, J. C. K.; Rowland, Malcolm

doi:10.1002/jps.2600570125

Cited by 163 publications

(62 citation statements)

References 7 publications

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“…The plot of plasma C-T was fit to two-compartment open model that has been described by (Riegelman et al 1968). This was on the basis of that the C-T curve was described by a bi-exponential equation and cannot be converted to a single straight line by converting plasma concentrations to the logarithmic domain as in occasion of one compartment open model.…”

Section: I) Single Intravenous Bolusmentioning

confidence: 99%

Pharmacokinetics of clarithromycin after single intravenous and intracrop bolus administrations to broiler chickens

AwadAllah

Awidat

El-Mahmoudy

2016

IJPT

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The pharmacokinetics of clarithromycin at a dose of 7.5 mg/kg body weight was evaluated after single intravenous (i.v.) and intracrop (i.c.) bolus administrations in broilers. An HPLC assay using pure clarithromycin base as a standard was used to measure its concentrations in plasma. Following an i.v. bolus injection, the plasma concentration-time curves of clarithromycin were best represented by twocompartment open models. The drug was rapidly distributed and moderately eliminated with half-lives of distribution (t 1/2α ) and elimination (t 1/2β ) of 0.38 and 4.58 h, respectively. The volume of distribution was large with (V dss ) value of 6.89 L. The total body clearance (Cl B ) was 1.2 L/h. After i.c. bolus administration of the same dose, clarithromycin was moderately absorbed in broilers with an intermediate absorption half-life (T ½ab ) of 0.72 h with peak plasma concentration (C max ) of 1.69 μg/ml attained at 1.7 h (T max ) and systemic bioavailability of 66.54%. The elimination half-life following i.c. administration was 2.11 h. The extent of plasma protein binding percent was 52%. The study recommends the use of clarithromycin in broilers because of its good pharmacokinetic profile indicated by good absorption, bioavailability and plasma concentrations ≥ MICs of many sensitive microorganisms.

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Section: I) Single Intravenous Bolusmentioning

confidence: 99%

Pharmacokinetics of clarithromycin after single intravenous and intracrop bolus administrations to broiler chickens

AwadAllah

Awidat

El-Mahmoudy

2016

IJPT

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“…In the single injection experiments, the initial volume of distribution (V1) of the injected cyclic nucleotide-3H was calculated (18,19). In the constant infusion studies, the "final" apparent volume of distribution (Vdinf eq) of the infused cyclic nucleotide-'H was calculated by the infusion equilibrium method (18,20). Estimates of extracellular fluid volume as measured by inulin space (Vdi.)…”

Section: Ancillary Analysesmentioning

confidence: 99%

“…The plasma clearance rate (PCR), frequently referred to as the metabolic clearance rate, represents the volume of plasma completely and irreversibly cleared of cyclic nucleotide-3H in unit time by all processes of metabolism and excretion. The PCR was calculated for both the injection and infusion studies by standard equations (18,25,26) and was subdivided into renal (Cr) and extrarenal or metabolic (Cm) clearances. The corresponding rates (nmoles per minute) of total (rei), renal (r,), and extrarenal or metabolic (rm) elimination of the cyclic nucleotides from plasma were given by the product of the appropriate clearance term and the plasma level of endogenous cyclic nucleotide.…”

Section: Ancillary Analysesmentioning

confidence: 99%

“…The values determined by the plasma method ranged from 6.6 to 12.7 nmoles/min with an average of 8.5 nmoles/min, or approximately 35% less than the average cyclic AMP production rate determined in similar fashion. (Table V) and 18.6%o for the infusion study (Table IV). DISCUSSION -Clearances and sources of the urinary cyclic nucleotides.…”

Section: Cyclic Amp and Cyclic Gmp In Man 2225mentioning

confidence: 99%

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Kinetic parameters and renal clearances of plasma adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate in man

Broadus¹,

Kaminsky²,

Hardman³

et al. 1970

J. Clin. Invest.

253

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A B S T R A C T Kinetic parameters and the renal clearances of plasma adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) were evaluated in normal subjects using tritium-labeled cyclic nucleotides. Each tracer was administered both by single, rapid intravenous injection and by constant intravenous infusion, and the specific activities of the cyclic nucleotides in plasma and urine were determined.Both cyclic AMP and cyclic GMP were cleared from plasma by glomerular filtration. The kidney was found to add a variable quantity of endogenous cyclic AMP to the tubular urine, amounting to an average of approximately one-third of the total level of cyclic AMP excreted. Plasma was the source of virtually all of the cyclic GMP excreted.Plasma levels of the cyclic nucleotides appeared to be in dynamic steady state. The apparent volumes of distribution of both nucleotides exceeded extracellular fluid volume, averaging 27 and 38% of body weight for cyclic AMP and cyclic GMP, respectively. Plasma production rates ranged from 9 to 17 nmoles/min for cyclic AMP and from 7 to 13 nnmoles/min for cyclic GMP. Plasma clearance rates averaged 668 mln/in for cyclic AMP and 855 ml/min for cyclic GMP. Approximately 85% of the elimination of the cyclic nucleotides from the circulation was due to extrarenal clearance.These studies were presented in part at the Annual Meeting of the Southern Society for Clinical Investigation, New Orleans, La., January, 1970. Clin. Res. 18: 73. (Abstr.) INTRODUCTION Adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) were identified in urine several years ago (1-3), but definitive studies concerning the sources of the excreted cyclic nucleotides have not been reported. Cyclic AMP has been found in dog plasma (1), and we have identified both cyclic nucleotides in human plasma, raising the possibility that renal plasma clearance could account for at least a portion of the cyclic nucleotides excreted into the urine. Two hormones known to stimulate renal adenyl cyclase systems (4) have been reported to increase cyclic AMP excretion (5, 6) suggesting the kidney as a source of urinary cyclic AMP. Similarly, the kidney has been suggested as a source of urinary cyclic GMP (7). In the absence of definitive clearance studies, it has not been possible to know whether the cyclic nucleotides in urine are derived solely from the kidney, solely from plasma, or both from plasma and from the kidney.The present studies were designed to evaluate the renal clearances as well as other kinetic parameters of the extracellular cyclic nucleotides. Tracer doses of tritiumlabeled cyclic nucleotides were administered to human subjects by rapid intravenous injection and by constant intravenous infusion. Specific radioactivity determinations of the cyclic nucleotides in plasma and urine provided information regarding the sources of cyclic AMP and cyclic GMP excreted into the urine. The effects of certain hormones on plasma and urinary cyclic nucleotides are repo...

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“…The kinetic equations and the model describing the drug concentrations in plasma after i.v. and intramuscular administration were recently published (4,16,17,20). The intrinsic absorption rate was determined by the method of Loo and Riegelman (10).…”

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confidence: 99%

Comparative Pharmacokinetics and Metabolism of Cephapirin in Laboratory Animals and Humans

Cabana¹,

Harken²,

Hottendorf³

1976

Antimicrob Agents Chemother

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Comparative drug disposition studies in mice, rats, dogs, and humans indicate that cephapirin, a new semisynthetic cephalosporin antibiotic that exhibits broad-spectrum antimicrobial activity, is metabolized to desacetylcephapirin in these species. Pharmacokinetic analyses of the concentrations of cephapirin and desacetylcephapirin in plasma and urine reveal that the rate and extent of deacetylation decreases from rodents to dogs to humans. The kinetic analyses also suggest that the kidney performs a role not only in the excretion but also in the metabolism of cephapirin to desacetylcephapirin.Cephapirin, sodium 7-(pyrid-4-yl-thioacetamido)cephalosporante ( Fig. 1), is a new semisynthetic 7-aminocephalosporanic acid derivative that exhibits a broad spectrum of antimicrobial activity (2,3,5) and in humans exhibits a similar pharmacokinetic profile to that of cephalothin (1). These results (1) were based on total bioactivity in serum, as determined by the cup-plate assay (6), and failed to take into account any possible differences in drug metabolism. In mice, rats, dogs, and humans, cephapirin has been shown to be metabolized to a bioactive desacetyl metabolite, and it has been suggested that the kidney performs a role not only in the excretion of the parent compound and desacetyl metabolite but also in the metabolism of cephapirin to desacetylcephapirin (B. E. Cabana and D. R. Van Harken, 5th Int. Congr., Pharmacol., San Francisco, Calif., Abstr. 209, p. 35, 1972 metabolism cages. In dogs, blood samples were taken from the saphenous vein by means of an intravenous (i.v.) catheter (Bardic, Intercath). The dogs were fasted overnight and hydrated (30 ml/kg) 15 to 30 min prior to drug administration. Continuous urine collection was achieved by means of Lucitecoated, stainless-steel cannulae surgically implanted within the bladder of the female dogs. The bladder cannulae were permanently implanted in dogs within 1 to 2 months of running the studies. The dogs had normal creatinine clearance (4 ml/min per kg) at the time of the study.Ten fasted, healthy male volunteers (mean weight, 66 kg) were employed for the human metabolic studies. The drug was administered by the i.v. route into the median cubital vein over a 5-min period. Blood specimens (20 ml) were drawn immediately before and at 5 min, 0.5, 1.0, 1.5, 2, 3, and 4 h after drug administration, and urine was collected at 1, 2, 4, and 6 h after drug administration. A water diuresis was maintained throughout the urine collection period by oral administration of 600 ml of tap water 20 min prior to drug administration and subsequent administration of 300 ml of water at 1 and 3 h after dosing.Blood specimens taken from the laboratory animals and men were placed in heparinized tubes (Vacutainers) and kept in an ice bath until centrifuged. Shortly thereafter, the blood specimens were spun down at approximately 1,000 x g in a refrigerated centrifuge (5°C), and the plasma samples were quickly frozen in a dry ice-acetone bath and kept frozen until bioassayed. The urine spe...

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Concept of a Volume of Distribution and Possible Errors in Evaluation of This Parameter

Cited by 163 publications

References 7 publications

Pharmacokinetics of clarithromycin after single intravenous and intracrop bolus administrations to broiler chickens

Pharmacokinetics of clarithromycin after single intravenous and intracrop bolus administrations to broiler chickens

Kinetic parameters and renal clearances of plasma adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate in man

Comparative Pharmacokinetics and Metabolism of Cephapirin in Laboratory Animals and Humans

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