Ampicillin and cephalexin in renal insufficiency

Hori, Ryohei; Okumura, Katsuhiko; Kamiya, Akira; Nihira, Hiromi; Nakano, Hiroshi

doi:10.1038/clpt.1983.251

Cited by 40 publications

(21 citation statements)

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“…Tmax CLus, mt-K, M + CI (11) where Tmax is the transport maximum (mass. time-1), CI is the concentration of unbound drug in the vicinity of tubular secretion sites, and K'M is the Michaelis constant (mass.…”

Section: The Definition Of Intrinsic Tubular Secretion Clearance and mentioning

confidence: 99%

“…Experimental [8] and clinical [4,9] data demonstrate that the renal clearance of a drug will approach zero in kidney failure, even if the drug is excreted by filtration and also by tubular secretion, which lends support to this hypothesis. On the other hand, there is some evidence that dosing adjustments based on simple proportionality of renal drug clearance to GFR may not be entirely adequate for certain drugs secreted in the tubules due to nonparallel behaviour of GFR and tubular secretion [10,11].…”

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confidence: 99%

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Physiological modelling of renal drug clearance

Jankü

1993

Eur J Clin Pharmacol

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A physiological model of renal drug clearance is presented with the aim of establishing a basis for adjusting drug dosing regimens in renal insufficiency. In agreement with the morphology of blood supply to the nephron, the model assumes serial arrangement of the processes involved in drug excretion. Fractional extraction by filtration in the glomeruli is defined in terms of the product of the unbound fraction of the drug, the filtration fraction being responsible for the limited extraction efficiency of this process. For a description of the limitations of the tubular secretory process by plasma flow through peritubular capillaries, the parallel tube model is utilized. The assumption of direct proportionality between the transport maximum of the secretory process and filtrate flow in the tubules permits a quantitative comparison of the intrinsic tubular secretion clearance and the effectiveness of the filtration process. Provided that the secretory mechanism is highly effective, renal clearance becomes dependent only on kidney plasma flow and the fraction of drug not reabsorbed in the tubules. Tubular reabsorption results only in a proportional decrease in renal clearance. The model predicts proportionality of renal drug clearance to GFR, which as a rule is used for dosage adjustment of drugs in renal insufficiency, only for compounds exclusively excreted by filtration. Compounds also excreted by tubular secretion in general exhibit a curvilinear relationship. The curvature is less pronounced as an increasing fraction of the drug is protein bound in blood. Therefore, for dosage adjustment of drugs secreted in the tubules and highly bound in blood, proportionality between renal clearance and GFR can serve as a reasonable approximation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: The Definition Of Intrinsic Tubular Secretion Clearance and mentioning

confidence: 99%

mentioning

confidence: 99%

Physiological modelling of renal drug clearance

Jankü

1993

Eur J Clin Pharmacol

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“…Creatinine, being cleared mainly by glomerular filtration, provides direct information only on the capacity for glomerular filtration but in many circumstances may correlate poorly with the other func tions o f the nephron, namely, tubular secretion and reab sorption. Because o f this limitation, several compounds have been investigated for their ability to measure the secretory capacity o f the kidney; these include p-aminohippuric acid [2], phenolsulphonephthalein [3] and tetraethylammonium [4], However, these substances are all ex ogenous and therefore need to be infused. In addition, for organic anions such as p-aminohippurate, other anions that can accumulate in uraemic blood may inhibit the renal tubular secretion o f the marker [5].…”

Section: Introductionmentioning

confidence: 99%

Estimation of Renal Tubular Secretion in Man, in Health and Disease, Using Endogenous N-1-Methylnicotinamide

Maiza

Waldek

Ballardie

et al. 1992

Nephron

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We have been investigating the possibility of using the renal clearance of endogenous N-1-methylnicotinamide (NMN) as a marker of renal tubular function. Sixty-three subjects (11 healthy volunteers and 52 patients with renal impairment) were used for this study. The subjects were divided into three groups according to their creatinine clearance: group 1, over 80 ml/min; group 2, between 30 and 80 ml/min, and group 3, less than 30 ml/min. The correlation between NMN and creatinine clearance was compared for each group. A good correlation (r = 0.84) was found for groups 1 and 3 (r = 0.76), whereas for group 2, a poor correlation was found (r = 0.43). For subjects with mild renal impairment (group 2), there was clear evidence of glomerulo-tubular imbalance manifest by a larger variability in NMN clearance than creatinine clearance and an essentially non-parallel decline in these two parameters for this group. When all subjects were grouped together, the relationship between the clearance of NMN and of creatinine was best described by a 3-term polynomial equation (r = 0.93). NMN clearance is a potentially useful non-invasive marker of renal tubular function in man and provides additional information to that provided by the measurement of creatinine clearance alone. This substance should be more fully evaluated as a potential diagnostic aid.

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“…Marre et al [11] and Toyoguchi and Nakagawa [12] reported that imipenem-cilastatin, flomoxef or fosfomycin may decrease the nephrotoxicity of VCM by inhibiting into the kidney. However, the interactions among LVFX and VCM are not clear [11][12][13][14]. Therefore, we studied the changes in the pharmacokinetics of LVFX and VCM when both agents were administered concomitantly to rats.…”

Section: Introductionmentioning

confidence: 99%

Interaction between Levofloxacin and Vancomycin in Rats – Study of Serum and Organ Levels

et al. 1998

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The changes of pharmacokinetic parameters when levofloxacin (LVFX) and vancomycin (VCM) were administered concomitantly were studied in rats. There was an increase in the AUC and T_max of LVFX with concomitant administration, but no effect on C_max. There was also an increase in the AUC and T_½ of VCM with concomitant administration, while V_d was reduced. Concomitant administration had no effect on the correlation between the serum and hepatic tissue concentrations of LVFX, but it markedly decreased the correlation between the serum and renal tissue concentrations of VCM. BUN was increased at 8 h after the administration of VCM. There have been reports that renal dysfunction can be caused by VCM, and our findings suggested that concomitant administration of LVFX and VCM must be performed with caution.

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Ampicillin and cephalexin in renal insufficiency

Cited by 40 publications

References 0 publications

Physiological modelling of renal drug clearance

Physiological modelling of renal drug clearance

Estimation of Renal Tubular Secretion in Man, in Health and Disease, Using Endogenous N-1-Methylnicotinamide

Interaction between Levofloxacin and Vancomycin in Rats – Study of Serum and Organ Levels

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