Prospective evaluation of a model for the prediction of milk:plasma drug concentrations from physicochemical characteristics.

Begg, EJ; Atkinson, Helen C.; Duffull, Stephen B.

doi:10.1111/j.1365-2125.1992.tb04077.x

Cited by 104 publications

(63 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, for a drug such as sumatriptan which has a short t I j z and delayed time of peak, such calculations will yield highly variable time-dependent values. In such cases, calculation of the M:P ratio based on AUC data has been recommended to achieve reliable data [15][16][17]. In our study, M:P ratios calculated using AUC data for sumatriptan give a mean value of 4.9 which is high by comparison with values for most other basic drugs [14,18].…”

Section: Time (H)mentioning

confidence: 69%

“…This value also is approximately three times greater than the theoretical M:P ratio of 1.6, which can be calculated using the pH-partition hypothesis [ 191, with a pK, of 9.63 (tertiary N) and plasma and milk pH values of 7.4 and 7.2 respectively. If one modifies this calculation as suggested by Begg et al [16], a theoretical M:P ratio of 2.6 or approximately 50% of the observed value is obtained. The latter calculation is most affected by milk pH and predicts ratios varying from 4.7 to 25.4 for a pH range of 7 to 6.8 respectively.…”

Section: Time (H)mentioning

confidence: 92%

See 1 more Smart Citation

Distribution and excretion of sumatriptan in human milk

Wojnar-Horton

Hackett

Yapp

et al. 1996

Brit J Clinical Pharma

View full text Add to dashboard Cite

1 The excretion of a 6 mg subcutaneous dose of sumatriptan in breast milk was studied in five lactating volunteer subjects with a mean age of 27.6 years and a mean body weight of 75 kg. Drug concentrations in milk and plasma over the ensuing 8 h were measured by high‐performance liquid chromatography. 2 The mean milk:plasma ratio estimated from the areas under the milk and plasma concentration‐time curves (AUC) was 4.9 (95% CI 4.1–5.7), indicating a significant transfer of sumatriptan into the milk compartment. 3 The mean total recovery of drug in milk was estimated to be only 14.4 μg (95% CI 6.1–22.7 μg), or 0.24% of the 6 mg administered dose. On a weight‐adjusted basis this corresponded to a mean infant exposure of 3.5% of the maternal dose (95% CI 0.3–6.7%). 4 If oral bioavailability in the infant is similar to that in adults (14%), the weight‐adjusted infant dose is reduced to 0.49%. Furthermore, allowance for reduced clearance in the infant predicts an infant exposure varying from 4.9% in a very premature neonate to 0.7% in a 30 week old infant. 5 Since sumatriptan is usually administered as a single dose at infrequent intervals, the low level of excretion in breast milk suggests that continued breast feeding following its use will not pose a significant risk to the suckling infant. Even this minor exposure could be largely avoided by expressing and discarding all milk for 8 h after the dose.

show abstract

Section: Time (H)mentioning

confidence: 69%

Section: Time (H)mentioning

confidence: 92%

Distribution and excretion of sumatriptan in human milk

Wojnar-Horton

Hackett

Yapp

et al. 1996

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…It is now possible to predict M/P ratios from the physicochemical characteristics of drugs [5,9]. Hence, an initial estimate of El can be calculated simply from equations (3) and (4) b) The measured highest M/P ratios of 74 drugs; 80% have M/P ratios of less than 1. c) Observed infant exposure (EIA) of 144 drugs derived from measured peak drug concentrations in milk; 90% have El A values of less than 10% of those expected after direct therapeutic doses.…”

Section: Resultsmentioning

confidence: 99%

A novel index for expressing exposure of the infant to drugs in breast milk.

Itô

Koren

1994

Brit J Clinical Pharma

View full text Add to dashboard Cite

parameter, i.e. milk-to-maternal plasma drug concentration ratio (M/P ratio).2 During breast-feeding by a woman receiving therapeutic doses of a drug at steady state this index is given by:where A is a coefficient (10 ml kg-l min-') and CL1 is drug clearance in the infant (ml kg-l min-). 3 This equation indicates a hyperbolic relationship between drug clearance and the exposure level of the breast-fed infant at a given M/P ratio of drug, emphasizing the importance of drug clearance as a determinant of infant exposure.

show abstract

“…The model was subsequently modified in an attempt to account for instances in which predicted M:P ratios differed from in vivo observations [4]. In a direct comparison of mathematical predictions, the log transformed model performed better than the other derivations but still over-or under-predicted the M:P ratio by >20% for 7 out of 10 drugs [8].…”

Section: Discussionmentioning

confidence: 99%

“…Other derived mathematical expressions have been reported [1][2][3]. Although an improvement on the H-H equation, these are not good predictors for all drugs [4]. Mathematical models that rely on published norms also fail to accommodate variation in the composition of the milk.…”

Section: Introductionmentioning

confidence: 99%